renaming BioC XML files to show PMC ID as file name and to be able to distinguish between raw and annotated XML; add folder with JSON version of annotated BioC

LICENSE.md

@@ -0,0 +1,9 @@
+MIT License
+
+Copyright (c) 2023, Melanie Vollmar
+
+Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the “Software”), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions:
+
+The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software.
+
+THE SOFTWARE IS PROVIDED “AS IS”, WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE.

annotated_BioC_JSON/PMC4781976_ann.json

@@ -0,0 +1 @@
+[{"sourceid":"4781976","sourcedb":"","project":"","target":"","text":"Structure of the GAT domain of the endosomal adapter protein Tom1 Cellular homeostasis requires correct delivery of cell-surface receptor proteins (cargo) to their target subcellular compartments. The adapter proteins Tom1 and Tollip are involved in sorting of ubiquitinated cargo in endosomal compartments. Recruitment of Tom1 to the endosomal compartments is mediated by its GAT domain’s association to Tollip’s Tom1-binding domain (TBD). In this data article, we report the solution NMR-derived structure of the Tom1 GAT domain. The estimated protein structure exhibits a bundle of three helical elements. We compare the Tom1 GAT structure with those structures corresponding to the Tollip TBD- and ubiquitin-bound states. Specifications table Table\t \t Subject area\tBiology\t \tMore specific subject area\tStructural biology\t \tType of data\tTable, text file, graph, figures\t \tHow data was acquired\tCircular dichroism and NMR. NMR data was recorded using a Bruker 800 MHz\t \tData format\tPDB format text file. Analyzed by CS-Rosetta, Protein Structure Validation Server (PSVS), NMRPipe, NMRDraw, and PyMol\t \tExperimental factors\tRecombinant human Tom1 GAT domain was purified to homogeneity before use\t \tExperimental features\tSolution structure of Tom1 GAT was determined from NMR chemical shift data\t \tData source location\tVirginia and Colorado, United States.\t \tData accessibility\tData is available within this article. Tom1 GAT structural data is publicly available in the RCSB Protein Data Bank (http://www.rscb.org/) under the accession number PDB: 2n9d\t \t Value of the data The Tom1 GAT domain solution structure will provide additional tools for modulating its biological function. Tom1 GAT can adopt distinct conformations upon ligand binding. A conformational response of the Tom1 GAT domain upon Tollip TBD binding can serve as an example to explain mutually exclusive ligand binding events. Data Analysis of the far-UV circular dichroism (CD) spectrum of the Tom 1 GAT domain (Fig. 1) predicts 58.7% α-helix, 3% β-strand, 15.5% turn, and 22.8% disordered regions. The Tom1 GAT structural restraints yielded ten helical structures (Fig. 2A,B) with a root mean square deviation (RMSD) of 0.9 Å for backbone and 1.3 Å for all heavy atoms (Table 1) and estimated the presence of three helices spanning residues Q216-E240 (α-helix 1), P248-Q274 (α-helix 2), and E278-T306 (α-helix 3). Unlike ubiquitin binding, data suggest that conformational changes of the Tom1 GAT α-helices 1 and 2 occur upon Tollip TBD binding (Fig. 3A,B). Experimental design, materials, and methods Protein expression and purification Human Tom1 GAT (residues 215–309) cDNA was cloned into both pGEX6P1 and pET28a vectors, and expressed as GST-tagged and His-tagged fusion proteins, respectively, using Escherichia coli [Rosetta (DE3) strain]. The 13C, 15N-labeled Tom1 GAT domain was expressed and purified as described previously. Circular dichroism Far-UV CD spectra of the His-Tom1 GAT domain were collected on a Jasco J-815 spectropolarimeter using a 1 mm path length quartz cell at room temperature. The protein (10 μM) was solubilized in 5 mM Tris–HCl (pH 7) and 100 mM KF. Spectra were obtained from five accumulated scans from 190 to 260 nm using a bandwidth of 1 nm and a response time of 1 s at a scan speed of 20 nm/min. Buffer backgrounds were employed to subtract the protein spectra. Data was processed using the Dichroweb server and the CONTIN algorithm (http://dichroweb.cryst.bbk.ac.uk/html/home.shtml). NMR structure determination NMR experiments were performed using 1 mM 13C, 15N-labeled Tom1 GAT domain in a buffer containing 20 mM d11-TrisHCl (pH 7), 50 mM KCl, 1 mM d18-DTT, and 1 mM NaN3. NMR spectra were recorded at 25 °C on a Bruker 800-MHz spectrometer (University of Virginia). The individual structure of Tom1 GAT was generated using CS-Rosetta (https://csrosetta.bmrb.wisc.edu/csrosetta). Chemical shift information (BMRB #26574) was used to obtain the structure calculation. The Rosetta calculations yielded 3000 structures of Tom1 GAT. From these, ten structures were selected based on their score and RMSDs, and converted to Protein Data Bank (PDB) format. NMR structural statistics for the ten lowest energy conformers of Tom1 GAT was generated using the Protein Structure Validation Suite. By using MolProbity, the Ramachandran analysis of the ten superimposed Tom1 GAT structures identified that 100% of the residues were in the most favored regions and there were no Ramachandran outliers in the allowed and disallowed regions. Protein structure images were obtained using PyMol (http://www.pymol.org). The structures of the ubiquitin- and Tollip TBD-bound states of the Tom1 GAT domain were obtained from data reported in Refs. and. References Tom1 modulates binding of Tollip to phosphatidylinositol 3-phosphate via a coupled folding and binding mechanism Structural basis for recognition of ubiquitinated cargo by Tom1-GAT domain Supplementary material Supplementary data associated with this article can be found in the online version at doi:10.1016/j.dib.2016.02.042. Representative far-UV CD spectrum of the His-Tom1 GAT domain. Fig. 1. (A) Stereo view displaying the best-fit backbone superposition of the refined structures for the Tom1 GAT domain. Helices are shown in orange, whereas loops are colored in green. (B) Ribbon illustration of the Tom1 GAT domain. Fig. 2. (A) Two views of the superimposed structures of the Tom1 GAT domain in the free state (gray) with that in the Tollip TBD-bound state (red). (B) Two views of the superimposed structures of the Tom1 GAT domain (gray) with that in the Ub-bound state (green). Fig. 3. NMR and refinement statistics for the Tom1 GAT domain. NMR structural statistics for lowest energy conformers of Tom1 GAT using PSVS. Table 1.\t \t \tTom1 GAT\t \tNMR distance and dihedral constraints\t\t \t Dihedral angle restraints total\t178\t \t ϕ\t89\t \t ψ\t89\t \tStructure statistics\t\t \t Dihedral angle constraints (deg)\t8.8±0.2\t \t Max. dihedral angle violation (deg)\t111±3\t \tDeviations from idealized geometry\t\t \t Bond lengths (Å)\t0.011\t \t Bond angles (deg)\t0.7\t \tAverage pairwise r.m.s. deviation (Å)a\t\t \t Protein\t\t \t Heavy\t1.3\t \t Backbone\t0.9\t \t Pairwise backbone and heavy-atom r.m.s. deviations were obtained by superimposing residues 215–309 of Tom1 GAT among 10 lowest energy refined structures.","denotations":[{"span":{"begin":0,"end":9},"obj":"0.9991358,evidence,cleaner0,2023-07-20T14:57:22Z,DUMMY:","id":"1"},{"span":{"begin":17,"end":20},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:58Z","id":"210"},{"span":{"begin":45,"end":60},"obj":"0.9416477,protein_type,cleaner0,2023-07-20T14:56:57Z,MESH:","id":"3"},{"span":{"begin":61,"end":65},"obj":"0.9997857,protein,cleaner0,2023-07-20T14:57:11Z,PR:","id":"4"},{"span":{"begin":116,"end":137},"obj":"0.8085951,protein_type,cleaner0,2023-07-20T14:56:52Z,MESH:","id":"5"},{"span":{"begin":201,"end":217},"obj":"0.99906075,protein_type,cleaner0,2023-07-20T14:57:01Z,MESH:","id":"6"},{"span":{"begin":218,"end":222},"obj":"0.99983084,protein,cleaner0,2023-07-20T14:57:11Z,PR:","id":"7"},{"span":{"begin":227,"end":233},"obj":"0.99978274,protein,cleaner0,2023-07-20T14:57:16Z,PR:","id":"8"},{"span":{"begin":261,"end":274},"obj":"0.96031576,ptm,cleaner0,2023-07-20T14:59:03Z,MESH:","id":"9"},{"span":{"begin":323,"end":327},"obj":"0.9998591,protein,cleaner0,2023-07-20T14:57:11Z,PR:","id":"10"},{"span":{"begin":377,"end":380},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:58Z","id":"209"},{"span":{"begin":405,"end":411},"obj":"0.99981624,protein,cleaner0,2023-07-20T14:57:16Z,PR:","id":"12"},{"span":{"begin":414,"end":433},"obj":"0.999658,structure_element,cleaner0,2023-07-20T14:57:32Z,SO:","id":"13"},{"span":{"begin":435,"end":438},"obj":"0.9997849,structure_element,cleaner0,2023-07-20T14:57:36Z,SO:","id":"14"},{"span":{"begin":477,"end":489},"obj":"0.9995477,experimental_method,cleaner0,2023-07-20T15:00:01Z,MESH:","id":"15"},{"span":{"begin":498,"end":507},"obj":"0.9994789,evidence,cleaner0,2023-07-20T14:57:22Z,DUMMY:","id":"16"},{"span":{"begin":515,"end":519},"obj":"0.9998665,protein,cleaner0,2023-07-20T14:57:11Z,PR:","id":"17"},{"span":{"begin":520,"end":523},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:58Z","id":"211"},{"span":{"begin":554,"end":563},"obj":"0.999076,evidence,cleaner0,2023-07-20T14:57:22Z,DUMMY:","id":"19"},{"span":{"begin":612,"end":619},"obj":"0.917164,experimental_method,cleaner0,2023-07-20T15:06:26Z,MESH:","id":"21"},{"span":{"begin":624,"end":628},"obj":"0.9998603,protein,cleaner0,2023-07-20T14:57:11Z,PR:","id":"22"},{"span":{"begin":629,"end":632},"obj":"0.99962676,structure_element,cleaner0,2023-07-20T14:57:58Z,SO:","id":"23"},{"span":{"begin":633,"end":642},"obj":"0.9995364,evidence,cleaner0,2023-07-20T14:57:22Z,DUMMY:","id":"24"},{"span":{"begin":654,"end":664},"obj":"0.9989391,evidence,cleaner0,2023-07-20T15:06:36Z,DUMMY:","id":"25"},{"span":{"begin":686,"end":692},"obj":"0.9998318,protein,cleaner0,2023-07-20T14:57:16Z,PR:","id":"26"},{"span":{"begin":693,"end":697},"obj":"0.9995357,protein_state,cleaner0,2023-07-20T14:58:41Z,DUMMY:","id":"27"},{"span":{"begin":702,"end":717},"obj":"0.9995535,protein_state,cleaner0,2023-07-20T14:58:47Z,DUMMY:","id":"28"},{"span":{"begin":901,"end":919},"obj":"0.99951756,experimental_method,cleaner0,2023-07-20T14:59:18Z,MESH:","id":"29"},{"span":{"begin":924,"end":927},"obj":"0.9996252,experimental_method,cleaner0,2023-07-20T14:59:32Z,MESH:","id":"30"},{"span":{"begin":929,"end":932},"obj":"0.99964654,experimental_method,cleaner0,2023-07-20T14:59:32Z,MESH:","id":"31"},{"span":{"begin":1022,"end":1032},"obj":"0.9992082,experimental_method,cleaner0,2023-07-20T15:06:30Z,MESH:","id":"32"},{"span":{"begin":1034,"end":1069},"obj":"0.9445149,experimental_method,cleaner0,2023-07-20T14:59:43Z,MESH:","id":"33"},{"span":{"begin":1071,"end":1075},"obj":"experimental_method,MESH:,cleaner0,2023-07-20T14:59:52Z","id":"237"},{"span":{"begin":1078,"end":1085},"obj":"0.97021425,experimental_method,cleaner0,2023-07-20T15:00:05Z,MESH:","id":"34"},{"span":{"begin":1087,"end":1094},"obj":"0.9534222,experimental_method,cleaner0,2023-07-20T15:00:07Z,MESH:","id":"35"},{"span":{"begin":1141,"end":1146},"obj":"0.99847716,species,cleaner0,2023-07-20T15:00:38Z,MESH:","id":"36"},{"span":{"begin":1147,"end":1151},"obj":"0.9998481,protein,cleaner0,2023-07-20T14:57:11Z,PR:","id":"37"},{"span":{"begin":1152,"end":1155},"obj":"0.5058204,structure_element,cleaner0,2023-07-20T14:57:58Z,SO:","id":"38"},{"span":{"begin":1226,"end":1244},"obj":"0.99844825,evidence,cleaner0,2023-07-20T15:00:14Z,DUMMY:","id":"39"},{"span":{"begin":1248,"end":1252},"obj":"0.99984014,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"40"},{"span":{"begin":1253,"end":1256},"obj":"0.98831964,structure_element,cleaner0,2023-07-20T14:57:58Z,SO:","id":"41"},{"span":{"begin":1277,"end":1280},"obj":"0.9996598,experimental_method,cleaner0,2023-07-20T14:59:32Z,MESH:","id":"42"},{"span":{"begin":1281,"end":1295},"obj":"evidence,DUMMY:,cleaner0,2023-07-20T15:00:28Z","id":"238"},{"span":{"begin":1422,"end":1426},"obj":"protein,PR:,cleaner0,2023-07-20T14:57:12Z","id":"193"},{"span":{"begin":1427,"end":1430},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:58Z","id":"212"},{"span":{"begin":1585,"end":1589},"obj":"0.99983656,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"45"},{"span":{"begin":1590,"end":1593},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:58Z","id":"213"},{"span":{"begin":1601,"end":1619},"obj":"0.9995917,evidence,cleaner0,2023-07-20T15:00:14Z,DUMMY:","id":"47"},{"span":{"begin":1690,"end":1694},"obj":"0.999843,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"48"},{"span":{"begin":1695,"end":1698},"obj":"0.9992766,structure_element,cleaner0,2023-07-20T14:57:58Z,SO:","id":"49"},{"span":{"begin":1786,"end":1790},"obj":"0.99981683,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"50"},{"span":{"begin":1791,"end":1794},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:58Z","id":"214"},{"span":{"begin":1807,"end":1813},"obj":"0.9990669,protein,cleaner0,2023-07-20T14:57:16Z,PR:","id":"52"},{"span":{"begin":1814,"end":1817},"obj":"0.99973947,structure_element,cleaner0,2023-07-20T14:57:36Z,SO:","id":"53"},{"span":{"begin":1924,"end":1949},"obj":"0.99765813,experimental_method,cleaner0,2023-07-20T15:01:25Z,MESH:","id":"54"},{"span":{"begin":1951,"end":1953},"obj":"0.97389156,experimental_method,cleaner0,2023-07-20T15:01:22Z,MESH:","id":"55"},{"span":{"begin":1955,"end":1963},"obj":"0.9930906,evidence,cleaner0,2023-07-20T15:01:19Z,DUMMY:","id":"56"},{"span":{"begin":1971,"end":1976},"obj":"0.99947125,protein,cleaner0,2023-07-20T15:06:22Z,PR:","id":"57"},{"span":{"begin":1977,"end":1980},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:58Z","id":"215"},{"span":{"begin":2012,"end":2019},"obj":"0.999609,structure_element,cleaner0,2023-07-20T15:01:58Z,SO:","id":"59"},{"span":{"begin":2024,"end":2032},"obj":"0.9994879,structure_element,cleaner0,2023-07-20T15:01:59Z,SO:","id":"60"},{"span":{"begin":2080,"end":2084},"obj":"0.99985206,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"61"},{"span":{"begin":2085,"end":2088},"obj":"0.7947963,structure_element,cleaner0,2023-07-20T14:57:58Z,SO:","id":"62"},{"span":{"begin":2089,"end":2110},"obj":"0.9988989,evidence,cleaner0,2023-07-20T15:06:41Z,DUMMY:","id":"63"},{"span":{"begin":2131,"end":2141},"obj":"0.9295965,evidence,cleaner0,2023-07-20T15:06:45Z,DUMMY:","id":"64"},{"span":{"begin":2161,"end":2187},"obj":"0.9993277,evidence,cleaner0,2023-07-20T15:01:33Z,DUMMY:","id":"65"},{"span":{"begin":2189,"end":2193},"obj":"0.9996222,evidence,cleaner0,2023-07-20T15:01:36Z,DUMMY:","id":"66"},{"span":{"begin":2319,"end":2328},"obj":"0.9990892,residue_range,cleaner0,2023-07-20T15:01:42Z,DUMMY:","id":"67"},{"span":{"begin":2330,"end":2339},"obj":"0.9997021,structure_element,cleaner0,2023-07-20T15:01:49Z,SO:","id":"68"},{"span":{"begin":2342,"end":2351},"obj":"0.9991074,residue_range,cleaner0,2023-07-20T15:01:44Z,DUMMY:","id":"69"},{"span":{"begin":2353,"end":2362},"obj":"0.9997027,structure_element,cleaner0,2023-07-20T15:01:51Z,SO:","id":"70"},{"span":{"begin":2369,"end":2378},"obj":"0.99909496,residue_range,cleaner0,2023-07-20T15:01:46Z,DUMMY:","id":"71"},{"span":{"begin":2380,"end":2389},"obj":"0.99970627,structure_element,cleaner0,2023-07-20T15:01:53Z,SO:","id":"72"},{"span":{"begin":2399,"end":2408},"obj":"0.99831545,chemical,cleaner0,2023-07-20T15:07:05Z,CHEBI:","id":"73"},{"span":{"begin":2466,"end":2470},"obj":"0.99984026,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"74"},{"span":{"begin":2471,"end":2474},"obj":"0.99932325,structure_element,cleaner0,2023-07-20T14:57:58Z,SO:","id":"75"},{"span":{"begin":2475,"end":2492},"obj":"0.9996645,structure_element,cleaner0,2023-07-20T15:01:56Z,SO:","id":"76"},{"span":{"begin":2504,"end":2510},"obj":"0.9998336,protein,cleaner0,2023-07-20T14:57:16Z,PR:","id":"77"},{"span":{"begin":2511,"end":2514},"obj":"0.9960354,structure_element,cleaner0,2023-07-20T14:57:36Z,SO:","id":"78"},{"span":{"begin":5151,"end":5160},"obj":"0.99858,experimental_method,cleaner0,2023-07-20T15:03:56Z,MESH:","id":"151"},{"span":{"begin":5161,"end":5169},"obj":"0.71714723,evidence,cleaner0,2023-07-20T15:06:50Z,DUMMY:","id":"152"},{"span":{"begin":5177,"end":5181},"obj":"0.8865229,experimental_method,cleaner0,2023-07-20T15:04:25Z,MESH:","id":"153"},{"span":{"begin":5181,"end":5185},"obj":"0.9922563,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"154"},{"span":{"begin":5186,"end":5189},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:59Z","id":"225"},{"span":{"begin":5246,"end":5268},"obj":"0.9992467,experimental_method,cleaner0,2023-07-20T15:04:41Z,MESH:","id":"156"},{"span":{"begin":5284,"end":5294},"obj":"0.9941738,evidence,cleaner0,2023-07-20T15:06:54Z,DUMMY:","id":"157"},{"span":{"begin":5303,"end":5307},"obj":"0.9998486,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"158"},{"span":{"begin":5308,"end":5311},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:59Z","id":"226"},{"span":{"begin":5416,"end":5420},"obj":"0.99984694,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"160"},{"span":{"begin":5421,"end":5424},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:59Z","id":"227"},{"span":{"begin":5462,"end":5485},"obj":"0.9534955,experimental_method,cleaner0,2023-07-20T15:05:10Z,MESH:","id":"162"},{"span":{"begin":5493,"end":5497},"obj":"0.99984646,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"163"},{"span":{"begin":5498,"end":5501},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:59Z","id":"228"},{"span":{"begin":5516,"end":5520},"obj":"0.99965954,protein_state,cleaner0,2023-07-20T15:05:18Z,DUMMY:","id":"165"},{"span":{"begin":5551,"end":5557},"obj":"0.9996728,protein,cleaner0,2023-07-20T14:57:16Z,PR:","id":"166"},{"span":{"begin":5558,"end":5567},"obj":"0.99953216,protein_state,cleaner0,2023-07-20T15:05:15Z,DUMMY:","id":"167"},{"span":{"begin":5602,"end":5625},"obj":"0.9632287,experimental_method,cleaner0,2023-07-20T15:05:12Z,MESH:","id":"168"},{"span":{"begin":5633,"end":5637},"obj":"0.9998419,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"169"},{"span":{"begin":5638,"end":5641},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:59Z","id":"229"},{"span":{"begin":5673,"end":5681},"obj":"0.9995443,protein_state,cleaner0,2023-07-20T15:05:16Z,DUMMY:","id":"171"},{"span":{"begin":5705,"end":5708},"obj":"0.99963295,experimental_method,cleaner0,2023-07-20T14:59:32Z,MESH:","id":"172"},{"span":{"begin":5713,"end":5734},"obj":"0.9961254,evidence,cleaner0,2023-07-20T15:05:29Z,DUMMY:","id":"173"},{"span":{"begin":5743,"end":5747},"obj":"0.9998447,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"174"},{"span":{"begin":5748,"end":5751},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:59Z","id":"230"},{"span":{"begin":5760,"end":5763},"obj":"0.999608,experimental_method,cleaner0,2023-07-20T14:59:32Z,MESH:","id":"176"},{"span":{"begin":5764,"end":5785},"obj":"0.9994303,evidence,cleaner0,2023-07-20T15:05:33Z,DUMMY:","id":"177"},{"span":{"begin":5818,"end":5822},"obj":"0.99985063,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"178"},{"span":{"begin":5823,"end":5826},"obj":"0.9986708,structure_element,cleaner0,2023-07-20T14:57:59Z,SO:","id":"179"},{"span":{"begin":5833,"end":5837},"obj":"0.9996277,experimental_method,cleaner0,2023-07-20T15:05:31Z,MESH:","id":"180"},{"span":{"begin":6294,"end":6311},"obj":"0.9994108,evidence,cleaner0,2023-07-20T15:05:50Z,DUMMY:","id":"187"},{"span":{"begin":6329,"end":6342},"obj":"0.99964523,experimental_method,cleaner0,2023-07-20T15:05:52Z,MESH:","id":"188"},{"span":{"begin":6352,"end":6359},"obj":"0.9990513,residue_range,cleaner0,2023-07-20T15:05:56Z,DUMMY:","id":"189"},{"span":{"begin":6363,"end":6367},"obj":"0.99986255,protein,cleaner0,2023-07-20T14:57:12Z,PR:","id":"190"},{"span":{"begin":6368,"end":6371},"obj":"structure_element,SO:,cleaner0,2023-07-20T14:57:59Z","id":"232"},{"span":{"begin":6403,"end":6413},"obj":"0.9991259,evidence,cleaner0,2023-07-20T15:06:59Z,DUMMY:","id":"191"}],"relations":[]}]

annotated_BioC_JSON/PMC4871749_ann.json

@@ -0,0 +1 @@
+[{"sourceid":"4871749","sourcedb":"","project":"","target":"","text":"The Taf14 YEATS domain is a reader of histone crotonylation The discovery of new histone modifications is unfolding at startling rates, however, the identification of effectors capable of interpreting these modifications has lagged behind. Here we report the YEATS domain as an effective reader of histone lysine crotonylation – an epigenetic signature associated with active transcription. We show that the Taf14 YEATS domain engages crotonyllysine via a unique π-π-π-stacking mechanism and that other YEATS domains have crotonyllysine binding activity. Crotonylation of lysine residues (crotonyllysine, Kcr) has emerged as one of the fundamental histone post-translational modifications (PTMs) found in mammalian chromatin. This epigenetic PTM is widespread and enriched at active gene promoters and potentially enhancers. The crotonyllysine mark on histone H3K18 is produced by p300, a histone acetyltransferase also responsible for acetylation of histones. Owing to some differences in their genomic distribution, the crotonyllysine and acetyllysine (Kac) modifications have been linked to distinct functional outcomes. p300-catalyzed histone crotonylation, which is likely metabolically regulated, stimulates transcription to a greater degree than p300-catalyzed acetylation. The discovery of individual biological roles for the crotonyllysine and acetyllysine marks suggests that these PTMs can be read by distinct readers. While a number of acetyllysine readers have been identified and characterized, a specific reader of the crotonyllysine mark remains unknown (reviewed in). A recent survey of bromodomains (BDs) demonstrates that only one BD associates very weakly with a crotonylated peptide, however it binds more tightly to acetylated peptides, inferring that bromodomains do not possess physiologically relevant crotonyllysine binding activity. The family of acetyllysine readers has been expanded with the discovery that the YEATS (Yaf9, ENL, AF9, Taf14, Sas5) domains of human AF9 and yeast Taf14 are capable of recognizing the histone mark H3K9ac. The acetyllysine binding function of the AF9 YEATS domain is essential for the recruitment of the histone methyltransferase DOT1L to H3K9ac-containing chromatin and for DOT1L-mediated H3K79 methylation and transcription. Similarly, activation of a subset of genes and DNA damage repair in yeast require the acetyllysine binding activity of the Taf14 YEATS domain. Consistent with its role in gene regulation, Taf14 was identified as a core component of the transcription factor complexes TFIID and TFIIF. However, Taf14 is also found in a number of chromatin-remodeling complexes (i.e., INO80, SWI/SNF and RSC) and the histone acetyltransferase complex NuA3, indicating a multifaceted role of Taf14 in transcriptional regulation and chromatin biology. In this study, we identified the Taf14 YEATS domain as a reader of crotonyllysine that binds to histone H3 crotonylated at lysine 9 (H3K9cr) via a distinctive binding mechanism. We found that H3K9cr is present in yeast and is dynamically regulated. To elucidate the molecular basis for recognition of the H3K9cr mark, we obtained a crystal structure of the Taf14 YEATS domain in complex with H3K9cr5-13 (residues 5–13 of H3) peptide (Fig. 1, Supplementary Results, Supplementary Fig. 1 and Supplementary Table 1). The Taf14 YEATS domain adopts an immunoglobin-like β sandwich fold containing eight anti-parallel β strands linked by short loops that form a binding site for H3K9cr (Fig. 1b). The H3K9cr peptide lays in an extended conformation in an orientation orthogonal to the β strands and is stabilized through an extensive network of direct and water-mediated hydrogen bonds and a salt bridge (Fig. 1c). The most striking feature of the crotonyllysine recognition mechanism is the unique coordination of crotonylated lysine residue. The fully extended side chain of K9cr transverses the narrow tunnel, crossing the β sandwich at right angle in a corkscrew-like manner (Fig. 1b and Supplementary Figure 1b). The planar crotonyl group is inserted between Trp81 and Phe62 of the protein, the aromatic rings of which are positioned strictly parallel to each other and at equal distance from the crotonyl group, yielding a novel aromatic-amide/aliphatic-aromatic π-π-π-stacking system that, to our knowledge, has not been reported previously for any protein-protein interaction (Fig. 1d and Supplementary Fig. 1c). The side chain of Trp81 appears to adopt two conformations, one of which provides maximum π-stacking with the alkene functional group while the other rotamer affords maximum π-stacking with the amide π electrons (Supplementary Fig. 1c). The dual conformation of Trp81 is likely due to the conjugated nature of the C=C and C=O π-orbitals within the crotonyl functional group. In addition to π-π-π stacking, the crotonyl group is stabilized by a set of hydrogen bonds and electrostatic interactions. The π bond conjugation of the crotonyl group gives rise to a dipole moment of the alkene moiety, resulting in a partial positive charge on the β-carbon (Cβ) and a partial negative charge on the α-carbon (Cα). This provides the capability for the alkene moiety to form electrostatic contacts, as Cα and Cβ lay within electrostatic interaction distances of the carbonyl oxygen of Gln79 and of the hydroxyl group of Thr61, respectively. The hydroxyl group of Thr61 also participates in a hydrogen bond with the amide nitrogen of the K9cr side chain (Fig. 1d). The fixed position of the Thr61 hydroxyl group, which facilitates interactions with both the amide and Cα of K9cr, is achieved through a hydrogen bond with imidazole ring of His59. Extra stabilization of K9cr is attained by a hydrogen bond formed between its carbonyl oxygen and the backbone nitrogen of Trp81, as well as a water-mediated hydrogen bond with the backbone carbonyl group of Gly82 (Fig 1d). This distinctive mechanism was corroborated through mapping the Taf14 YEATS-H3K9cr binding interface in solution using NMR chemical shift perturbation analysis (Supplementary Fig. 2a, b). Binding of the Taf14 YEATS domain to H3K9cr is robust. The dissociation constant (Kd) for the Taf14 YEATS-H3K9cr5-13 complex was found to be 9.5 μM, as measured by fluorescence spectroscopy (Supplementary Fig. 2c). This value is in the range of binding affinities exhibited by the majority of histone readers, thus attesting to the physiological relevance of the H3K9cr recognition by Taf14. To determine whether H3K9cr is present in yeast, we generated whole cell extracts from logarithmically growing yeast cells and subjected them to Western blot analysis using antibodies directed towards H3K9cr, H3K9ac and H3 (Fig. 2a, b, Supplementary Fig. 3 and Supplementary Table 2). Both H3K9cr and H3K9ac were detected in yeast histones; to our knowledge, this is the first report of H3K9cr occurring in yeast. We next asked if H3K9cr is regulated by the actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Towards this end, we probed extracts derived from yeast cells in which major yeast HATs (HAT1, Gcn5, and Rtt109) or HDACs (Rpd3, Hos1, and Hos2) were deleted. As shown in Figure 2a, b and Supplementary Fig. 3e, H3K9cr levels were abolished or reduced considerably in the HAT deletion strains, whereas they were dramatically increased in the HDAC deletion strains. Furthermore, fluctuations in the H3K9cr levels were more substantial than fluctuations in the corresponding H3K9ac levels. Together, these results reveal that H3K9cr is a dynamic mark of chromatin in yeast and suggest an important role for this modification in transcription as it is regulated by HATs and HDACs. We have previously shown that among acetylated histone marks, the Taf14 YEATS domain prefers acetylated H3K9 (also see Supplementary Fig. 3b), however it binds to H3K9cr tighter. The selectivity of Taf14 towards crotonyllysine was substantiated by 1H,15N HSQC experiments, in which either H3K9cr5-13 or H3K9ac5-13 peptide was titrated into the 15N-labeled Taf14 YEATS domain (Fig. 2c and Supplementary Fig. 4a, b). Binding of H3K9cr induced resonance changes in slow exchange regime on the NMR time scale, indicative of strong interaction. In contrast, binding of H3K9ac resulted in an intermediate exchange, which is characteristic of a weaker association. Furthermore, crosspeaks of Gly80 and Trp81 of the YEATS domain were uniquely perturbed by H3K9cr and H3K9ac, indicating a different chemical environment in the respective crotonyllysine and acetyllysine binding pockets (Supplementary Fig. 4a). These differences support our model that Trp81 adopts two conformations upon complex formation with the H3K9cr mark as compared to H3K9ac (Supplementary Figs. 1c, d and 4c). One of the conformations, characterized by the π stacking involving two aromatic residues and the alkene group, is observed only in the YEATS-H3K9cr complex. To establish whether the Taf14 YEATS domain is able to recognize other recently identified acyllysine marks, we performed solution pull-down assays using H3 peptides acetylated, propionylated, butyrylated, and crotonylated at lysine 9 (residues 1–20 of H3). As shown in Figure 2d and Supplementary Fig. 5a, the Taf14 YEATS domain binds more strongly to H3K9cr1-20, as compared to other acylated histone peptides. The preference for H3K9cr over H3K9ac, H3K9pr and H3K9bu was supported by 1H,15N HSQC titration experiments. Addition of H3K9ac1-20, H3K9pr1-20, and H3K9bu1-20 peptides caused chemical shift perturbations in the Taf14 YEATS domain in intermediate exchange regime, implying that these interactions are weaker compared to the interaction with the H3K9cr1-20 peptide (Supplementary Fig. 5b). We concluded that H3K9cr is the preferred target of this domain. From comparative structural analysis of the YEATS complexes, Gly80 emerged as candidate residue potentially responsible for the preference for crotonyllysine. In attempt to generate a mutant capable of accommodating a short acetyl moiety but discriminating against a longer, planar crotonyl moiety, we mutated Gly80 to more bulky residues, however all mutants of Gly80 lost their binding activities towards either acylated peptide, suggesting that Gly80 is absolutely required for the interaction. In contrast, mutation of Val24, a residue located on another side of Trp81, had no effect on binding (Fig. 2d and Supplementary Fig. 5a, c). To determine if the binding to crotonyllysine is conserved, we tested human YEATS domains by pull-down experiments using singly and multiply acetylated, propionylated, butyrylated, and crotonylated histone peptides (Supplementary Fig. 6). We found that all YEATS domains tested are capable of binding to crotonyllysine peptides, though they display variable preferences for the acyl moieties. While YEATS2 and ENL showed selectivity for the crotonylated peptides, GAS41 and AF9 bound acylated peptides almost equally well. Unlike the YEATS domain, a known acetyllysine reader, bromodomain, does not recognize crotonyllysine. We assayed a large set of BDs in pull-down experiments and found that this module is highly specific for acetyllysine and propionyllysine containing peptides (Supplementary Fig. 7). However, bromodomains did not interact (or associated very weakly) with longer acyl modifications, including crotonyllysine, as in the case of BDs of TAF1 and BRD2, supporting recent reports. These results demonstrate that the YEATS domain is currently the sole reader of crotonyllysine. In conclusion, we have identified the YEATS domain of Taf14 as the first reader of histone crotonylation. The unique and previously unobserved aromatic-amide/aliphatic-aromatic π-π-π-stacking mechanism facilitates the specific recognition of the crotonyl moiety. We further demonstrate that H3K9cr exists in yeast and is dynamically regulated by HATs and HDACs. As we previously showed the importance of acyllysine binding by the Taf14 YEATS domain for the DNA damage response and gene transcription, it will be essential in the future to define the physiological role of crotonyllysine recognition and to differentiate the activities of Taf14 that are due to binding to crotonyllysine and acetyllysine modifications. Furthermore, the functional significance of crotonyllysine recognition by other YEATS proteins will be of great importance to elucidate and compare. ONLINE METHODS Protein expression and purification The Taf14 YEATS constructs (residues 1–132 or 1–137) were expressed in E. coli BL21 (DE3) RIL in either Luria Broth or M19 minimal media supplemented with 15NH4Cl and purified as N-terminal GST fusion proteins. Cells were harvested by centrifugation and resuspended in 50 mM HEPES (pH 7.5) supplemented with 150 mM NaCl and 1 mM TCEP. Cells are lysed by freeze-thaw followed by sonication. Proteins were purified on glutathione Sepharose 4B beads and the GST tag was cleaved with PreScission protease. X-ray data collection and structure determination Taf14 YEATS (residues 1–137) was concentrated to 9 mg/mL in 25 mM MES (pH 6.5) and incubated with 2 molar equivalence of the H3K9cr5-13 at RT for 30 mins prior to crystallization. Crystals were obtain via sitting drop diffusion method at 18°C by mixing 800 nL of protein/peptide solution with 800 nL of well solution composed of 44% PEG600 (v/v) and 0.2 M citric acid (pH 6.0). X-ray diffraction data was collected at a wavelength of 1.54 Å at 100 K from a single crystal on the UC Denver Biophysical Core home source composed of a Rigaku Micromax 007 high frequency microfocus X-ray generator with a Pilatus 200K 2D area detector. HKL3000 was used for indexing, scaling, and data reduction. Solution was solved via molecular replacement with Phaser using the Taf14 YEATS domain (PDB 5D7E) as search model with waters, ligands, and peptide removed. Phenix was used for refinement of structure and waters were manually placed by inception of difference maps in Coot. Ramachandran plot indicates good stereochemistry of the three-dimensional structure with 100% of all residues falling within the favored (98%) and allowed (2%) regions. The crystallographic statistics are shown in Supplementary Table 1. NMR spectroscopy NMR spectroscopy was carried out on a Varian INOVA 600 MHz spectrometer outfitted with a cryogenic probe. Chemical shift perturbation (CSP) analysis was performed using uniformly 15N-labeled Taf14 (1–132). 1H,15N heteronuclear single quantum coherence (HSQC) spectra of the Taf14 YEATS domain were collected in the presence of increasing concentrations of either H3K9cr5-13, H3K9ac5-13, H3K9cr1-20, H3K9ac1-20 H3K9pr1-20, H3K9bu1-20 or free Kcr in PBS buffer pH 6.8, 8% D2O. Fluorescence binding assays Tryptophan fluorescence measurements were performed on a Fluorolog spectrofluorometer at room temperature as described. The samples containing 2 μM of Taf14 YEATS in PBS (pH 7.4) and increasing concentrations of H3K9cr5-13 were excited at 295 nm. Emission spectra were recorded from 310 to 340 nm with a 1 nm step size and a 0.5 sec integration time. The Kd value was determined using a nonlinear least-squares analysis and the equation:   where [L] is the concentration of the peptide, [P] is the concentration of the protein, ΔI is the observed change of signal intensity, and ΔImax is the difference in signal intensity of the free and bound states. The Kd values were averaged over 3 separate experiments, with error calculated as the standard deviation (SD). Peptide pull-downs YEATS domains in pGEX vectors were expressed in SoluBL21 cells (Amsbio) by induction with 1 mM IPTG at 16–18°C overnight with shaking. Cells were lysed by freeze-thaw and sonication then purified over glutathione agarose (Pierce) in a buffer containing 50 mM Tris pH 8.0, 500 mM NaCl, 20% glycerol (v/v) and 1 mM dithiothreitol (DTT). Peptide pull-downs were performed essentially as described except that the assay buffer contained 50 mM Tris pH 8.0, 500 mM NaCl, and 0.1% NP-40, and 500 pmols of biotinylated histone peptides were loaded onto streptavidin coated magnetic beads before incubation with 40 pmols of protein. Bound proteins were detected with rabbit GST antibody (Sigma, G7781). Point mutants were generated by site-directed mutagenesis and purified/assayed as described above. The YEATS domains of Taf14, AF9, ENL, and GAS41 were previously described. Western blotting Yeast cultures were grown in YPD media at 30°C to mid-log phase and extracts were prepared as previously described. Proteins from cell lysates were separated by SDS-PAGE and transferred to a PVDF membrane. Anti-H3K9ac (Millipore, 07-352) and anti-H3K9cr (PTM Biolabs, PTM-516) were diluted to 1:2000 and 1:1000, respectively, in 1x Superblock (ThermoScientific). An HRP-conjugated anti-rabbit (GE Healthcare) was used for detection. Bands were quantified using the ImageJ program. Dot blotting Increasing concentrations of biotinylated histone peptides (0.06–1.5 μg) were spotted onto a PVDF membrane then probed with the anti-H3K9ac (Millipore, 07-352) or H3K9cr (PTM Biolabs, PTM-516) at 1:2000 in a 5% non-fat milk solution and detected with an HRP-conjugated anti-rabbit by enhanced chemiluminesence (ECL). Bromodomains pull-downs cDNAs of GST-fused bromodomains were obtained either from EpiCypher Inc. or as a kind gift from Katrin Chua (Stanford University). GST fusions were expressed as described above except that the preparation buffer contained 50 mM Tris (pH 7.5), 150 mM NaCl, 10% glycerol (v/v), and 1 mM DTT. Pull-down assays were preformed as described above except that the assay buffer contained 50 mM Tris (pH 8.0), 300 mM NaCl, and 0.1% NP-40. Supplementary Material Accession codes. Coordinates and structure factors have been deposited in the Protein Data Bank under accession codes 5IOK. Author contributions F.H.A., S.A.S., E.K.S., J.B.B., A.G., I.K.T and K.K. performed experiments and together with X.S., B.D.S and T.G.K. analyzed the data. F.H.A., S.A.S., B.D.S. and T.G.K. wrote the manuscript with input from all authors. Competing Financial Interest The authors declare no competing financial interests. Additional information Any supplementary information is available in the online version of this paper. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification Intracellular Crotonyl-CoA Stimulates Transcription through p300-Catalyzed Histone Crotonylation Protein lysine acylation and cysteine succination by intermediates of energy metabolism Identification of ‘erasers’ for lysine crotonylated histone marks using a chemical proteomics approach Perceiving the epigenetic landscape through histone readers Interpreting the language of histone and DNA modifications A Subset of Human Bromodomains Recognizes Butyryllysine and Crotonyllysine Histone Peptide Modifications Histone recognition and large-scale structural analysis of the human bromodomain family YEATS domain proteins: a diverse family with many links to chromatin modification and transcription AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation Association of Taf14 with acetylated histone H3 directs gene transcription and the DNA damage response Anc1 interacts with the catalytic subunits of the general transcription factors TFIID and TFIIF, the chromatin remodeling complexes RSC and INO80, and the histone acetyltransferase complex NuA3 Preparation and analysis of the INO80 complex TFG/TAF30/ANC1, a component of the yeast SWI/SNF complex that is similar to the leukemogenic proteins ENL and AF-9 The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex The essential role of acetyllysine binding by the YEATS domain in transcriptional regulation Phaser crystallographic software PHENIX: a comprehensive Python-based system for macromolecular structure solution Features and development of Coot Molecular basis for chromatin binding and regulation of MLL5 Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation Association of Taf14 with acetylated histone H3 directs gene transcription and the DNA damage response The Saccharomyces cerevisiae histone H2A variant Htz1 is acetylated by NuA4 A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery The structural mechanism for the recognition of H3K9cr (a) Chemical structure of crotonyllysine. (b) The crystal structure of the Taf14 YEATS domain (wheat) in complex with the H3K9cr5-13 peptide (green). (c) H3K9cr is stabilized via an extensive network of intermolecular electrostatic and polar interactions with the Taf14 YEATS domain. (d) The π-π-π stacking mechanism involving the alkene moiety of crotonyllysine. H3K9cr is a selective target of the Taf14 YEATS domain (a, b) Western blot analysis comparing the levels of H3K9cr and H3K9ac in wild type (WT), HAT deletion, or HDAC deletion yeast strains. Total H3 was used as a loading control. (c) Superimposed 1H,15N HSQC spectra of Taf14 YEATS recorded as H3K9cr5-13 and H3K9ac5-13 peptides were titrated in. Spectra are color coded according to the protein:peptide molar ratio. (d) Western blot analyses of peptide pull-down assays using wild-type and mutated Taf14 YEATS domains and indicated peptides.","denotations":[{"span":{"begin":4,"end":9},"obj":"0.99879897,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"1"},{"span":{"begin":10,"end":22},"obj":"0.9920379,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"2"},{"span":{"begin":38,"end":45},"obj":"0.9768092,protein_type,cleaner0,2023-07-04T16:21:00Z,MESH:","id":"3"},{"span":{"begin":46,"end":59},"obj":"0.60347056,ptm,cleaner0,2023-07-04T16:18:43Z,MESH:","id":"4"},{"span":{"begin":81,"end":88},"obj":"protein_type,MESH:,cleaner0,2023-07-04T16:21:00Z","id":"553"},{"span":{"begin":259,"end":271},"obj":"0.98157585,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"5"},{"span":{"begin":298,"end":305},"obj":"0.6092492,protein_type,cleaner0,2023-07-04T16:21:00Z,MESH:","id":"6"},{"span":{"begin":306,"end":312},"obj":"0.64678025,residue_name,cleaner0,2023-07-05T08:52:59Z,SO:","id":"7"},{"span":{"begin":313,"end":326},"obj":"0.7005873,ptm,cleaner0,2023-07-04T16:18:43Z,MESH:","id":"8"},{"span":{"begin":408,"end":413},"obj":"0.9987513,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"9"},{"span":{"begin":414,"end":426},"obj":"0.98611736,structure_element,cleaner0,2023-07-04T16:20:27Z,SO:","id":"10"},{"span":{"begin":435,"end":449},"obj":"0.99818015,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"11"},{"span":{"begin":463,"end":477},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"717"},{"span":{"begin":503,"end":516},"obj":"0.8457508,structure_element,cleaner0,2023-07-05T08:49:39Z,SO:","id":"12"},{"span":{"begin":522,"end":536},"obj":"residue_name,SO:,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z","id":"542"},{"span":{"begin":560,"end":573},"obj":"0.97012514,ptm,cleaner0,2023-07-04T16:18:43Z,MESH:","id":"13"},{"span":{"begin":577,"end":583},"obj":"0.8647513,residue_name,cleaner0,2023-07-05T08:53:04Z,SO:","id":"14"},{"span":{"begin":594,"end":608},"obj":"0.99726224,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"15"},{"span":{"begin":610,"end":613},"obj":"0.9968893,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"16"},{"span":{"begin":653,"end":660},"obj":"protein_type,MESH:,cleaner0,2023-07-04T16:21:00Z","id":"554"},{"span":{"begin":710,"end":719},"obj":"0.9958947,taxonomy_domain,cleaner0,2023-07-04T16:21:35Z,DUMMY:","id":"17"},{"span":{"begin":834,"end":848},"obj":"0.7653515,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"18"},{"span":{"begin":857,"end":864},"obj":"protein_type,MESH:,cleaner0,2023-07-04T16:21:00Z","id":"555"},{"span":{"begin":865,"end":867},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:36:55Z","id":"666"},{"span":{"begin":867,"end":870},"obj":"residue_name_number,DUMMY:,cleaner0,2023-07-05T08:37:14Z","id":"667"},{"span":{"begin":886,"end":890},"obj":"0.98865753,protein,cleaner0,2023-07-04T16:20:32Z,PR:","id":"20"},{"span":{"begin":894,"end":919},"obj":"0.98868376,protein_type,cleaner0,2023-07-04T16:22:54Z,MESH:","id":"21"},{"span":{"begin":941,"end":952},"obj":"0.7823207,ptm,cleaner0,2023-07-04T16:18:49Z,MESH:","id":"22"},{"span":{"begin":1027,"end":1041},"obj":"0.9841765,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"23"},{"span":{"begin":1046,"end":1058},"obj":"0.9894874,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"24"},{"span":{"begin":1060,"end":1063},"obj":"0.98921156,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"25"},{"span":{"begin":1129,"end":1133},"obj":"0.9711801,protein,cleaner0,2023-07-04T16:20:33Z,PR:","id":"26"},{"span":{"begin":1144,"end":1151},"obj":"protein_type,MESH:,cleaner0,2023-07-04T16:21:00Z","id":"557"},{"span":{"begin":1152,"end":1165},"obj":"0.9621592,ptm,cleaner0,2023-07-04T16:18:43Z,MESH:","id":"27"},{"span":{"begin":1258,"end":1262},"obj":"0.9124805,protein,cleaner0,2023-07-04T16:20:33Z,PR:","id":"28"},{"span":{"begin":1273,"end":1284},"obj":"0.87436926,ptm,cleaner0,2023-07-04T16:18:49Z,MESH:","id":"29"},{"span":{"begin":1339,"end":1353},"obj":"0.91712606,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"30"},{"span":{"begin":1358,"end":1370},"obj":"0.9561159,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"31"},{"span":{"begin":1453,"end":1465},"obj":"0.8240044,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"32"},{"span":{"begin":1539,"end":1553},"obj":"0.6335516,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"33"},{"span":{"begin":1609,"end":1621},"obj":"0.94788533,structure_element,cleaner0,2023-07-04T16:21:48Z,SO:","id":"34"},{"span":{"begin":1623,"end":1626},"obj":"0.8961469,structure_element,cleaner0,2023-07-04T16:21:53Z,SO:","id":"35"},{"span":{"begin":1655,"end":1657},"obj":"0.92061985,structure_element,cleaner0,2023-07-05T08:51:22Z,SO:","id":"36"},{"span":{"begin":1688,"end":1700},"obj":"0.9774638,protein_state,cleaner0,2023-07-04T16:22:06Z,DUMMY:","id":"37"},{"span":{"begin":1743,"end":1753},"obj":"0.98200285,protein_state,cleaner0,2023-07-04T16:22:11Z,DUMMY:","id":"39"},{"span":{"begin":1779,"end":1791},"obj":"0.7515075,structure_element,cleaner0,2023-07-04T16:21:48Z,SO:","id":"41"},{"span":{"begin":1832,"end":1846},"obj":"residue_name,SO:,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z","id":"543"},{"span":{"begin":1879,"end":1891},"obj":"0.9015483,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"42"},{"span":{"begin":1946,"end":1951},"obj":"0.9973253,structure_element,cleaner0,2023-07-05T08:51:28Z,SO:","id":"43"},{"span":{"begin":1953,"end":1957},"obj":"0.99829453,protein,cleaner0,2023-07-05T07:54:03Z,PR:","id":"44"},{"span":{"begin":1959,"end":1962},"obj":"0.99791545,protein,cleaner0,2023-07-05T07:54:08Z,PR:","id":"45"},{"span":{"begin":1964,"end":1967},"obj":"0.9983627,protein,cleaner0,2023-07-05T07:54:14Z,PR:","id":"46"},{"span":{"begin":1969,"end":1974},"obj":"0.9985991,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"47"},{"span":{"begin":1976,"end":1980},"obj":"0.9987198,protein,cleaner0,2023-07-05T07:54:25Z,PR:","id":"48"},{"span":{"begin":1993,"end":1998},"obj":"0.96409446,species,cleaner0,2023-07-04T16:22:25Z,MESH:","id":"49"},{"span":{"begin":1999,"end":2002},"obj":"0.99878556,protein,cleaner0,2023-07-05T07:54:15Z,PR:","id":"50"},{"span":{"begin":2007,"end":2012},"obj":"0.9893267,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"51"},{"span":{"begin":2013,"end":2018},"obj":"0.9988275,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"52"},{"span":{"begin":2050,"end":2057},"obj":"protein_type,MESH:,cleaner0,2023-07-04T16:21:00Z","id":"558"},{"span":{"begin":2063,"end":2065},"obj":"protein_type,MESH:,cleaner0,2023-07-05T07:55:54Z","id":"585"},{"span":{"begin":2065,"end":2069},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:53:13Z","id":"589"},{"span":{"begin":2075,"end":2087},"obj":"residue_name,SO:,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z","id":"547"},{"span":{"begin":2112,"end":2115},"obj":"0.99856865,protein,cleaner0,2023-07-05T07:54:15Z,PR:","id":"54"},{"span":{"begin":2116,"end":2128},"obj":"0.9379061,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"55"},{"span":{"begin":2169,"end":2194},"obj":"0.9904277,protein_type,cleaner0,2023-07-04T16:22:40Z,MESH:","id":"56"},{"span":{"begin":2195,"end":2200},"obj":"0.99846435,protein,cleaner0,2023-07-05T07:57:04Z,PR:","id":"57"},{"span":{"begin":2204,"end":2206},"obj":"protein_type,MESH:,cleaner0,2023-07-05T07:56:42Z","id":"590"},{"span":{"begin":2206,"end":2210},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T12:00:58Z","id":"591"},{"span":{"begin":2240,"end":2245},"obj":"0.9973254,protein,cleaner0,2023-07-05T07:57:04Z,PR:","id":"59"},{"span":{"begin":2255,"end":2257},"obj":"protein_type,MESH:,cleaner0,2023-07-05T07:57:26Z","id":"592"},{"span":{"begin":2257,"end":2260},"obj":"residue_name_number,DUMMY:,cleaner0,2023-07-05T07:57:40Z","id":"593"},{"span":{"begin":2261,"end":2272},"obj":"ptm,MESH:,cleaner0,2023-07-05T07:57:58Z","id":"594"},{"span":{"begin":2360,"end":2365},"obj":"0.9963744,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"61"},{"span":{"begin":2378,"end":2390},"obj":"residue_name,SO:,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z","id":"548"},{"span":{"begin":2415,"end":2420},"obj":"0.9987602,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"62"},{"span":{"begin":2421,"end":2433},"obj":"0.94719505,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"63"},{"span":{"begin":2480,"end":2485},"obj":"0.9980909,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"64"},{"span":{"begin":2559,"end":2564},"obj":"0.84213173,complex_assembly,cleaner0,2023-07-04T16:23:51Z,GO:","id":"67"},{"span":{"begin":2569,"end":2574},"obj":"0.6936775,complex_assembly,cleaner0,2023-07-04T16:24:02Z,GO:","id":"68"},{"span":{"begin":2585,"end":2590},"obj":"0.9974746,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"69"},{"span":{"begin":2658,"end":2663},"obj":"0.7698535,complex_assembly,cleaner0,2023-07-05T07:58:48Z,GO:","id":"71"},{"span":{"begin":2665,"end":2672},"obj":"0.67576855,complex_assembly,cleaner0,2023-07-05T07:58:53Z,GO:","id":"72"},{"span":{"begin":2677,"end":2680},"obj":"0.5300177,complex_assembly,cleaner0,2023-07-05T07:59:00Z,GO:","id":"73"},{"span":{"begin":2690,"end":2715},"obj":"0.8560897,protein_type,cleaner0,2023-07-04T16:22:53Z,MESH:","id":"74"},{"span":{"begin":2724,"end":2728},"obj":"0.77899855,complex_assembly,cleaner0,2023-07-05T08:50:53Z,GO:","id":"76"},{"span":{"begin":2764,"end":2769},"obj":"0.99761933,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"77"},{"span":{"begin":2856,"end":2861},"obj":"0.9986816,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"78"},{"span":{"begin":2862,"end":2874},"obj":"0.93180734,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"79"},{"span":{"begin":2890,"end":2904},"obj":"0.9986914,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"80"},{"span":{"begin":2919,"end":2926},"obj":"protein_type,MESH:,cleaner0,2023-07-04T16:21:00Z","id":"561"},{"span":{"begin":2927,"end":2929},"obj":"protein_type,MESH:,cleaner0,2023-07-05T07:55:54Z","id":"586"},{"span":{"begin":2930,"end":2942},"obj":"0.6754686,protein_state,cleaner0,2023-07-04T16:22:07Z,DUMMY:","id":"82"},{"span":{"begin":2946,"end":2954},"obj":"residue_name_number,DUMMY:,cleaner0,2023-07-05T07:58:27Z","id":"595"},{"span":{"begin":2956,"end":2958},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:00:12Z","id":"597"},{"span":{"begin":2958,"end":2962},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:52:22Z","id":"598"},{"span":{"begin":3015,"end":3017},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:00:12Z","id":"599"},{"span":{"begin":3017,"end":3021},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:52:32Z","id":"600"},{"span":{"begin":3036,"end":3041},"obj":"0.9966305,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"87"},{"span":{"begin":3128,"end":3130},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:00:50Z","id":"601"},{"span":{"begin":3130,"end":3134},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:52:40Z","id":"602"},{"span":{"begin":3155,"end":3172},"obj":"0.9973307,evidence,cleaner0,2023-07-05T08:56:20Z,DUMMY:","id":"89"},{"span":{"begin":3180,"end":3185},"obj":"0.9986278,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"90"},{"span":{"begin":3186,"end":3198},"obj":"0.9957862,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"91"},{"span":{"begin":3199,"end":3214},"obj":"0.9311703,protein_state,cleaner0,2023-07-05T08:53:17Z,DUMMY:","id":"92"},{"span":{"begin":3215,"end":3225},"obj":"0.97627616,chemical,cleaner0,2023-07-05T08:36:15Z,CHEBI:","id":"93"},{"span":{"begin":3236,"end":3240},"obj":"0.96639997,residue_range,cleaner0,2023-07-05T08:49:48Z,DUMMY:","id":"94"},{"span":{"begin":3244,"end":3246},"obj":"0.9895627,protein_type,cleaner0,2023-07-05T07:55:54Z,MESH:","id":"95"},{"span":{"begin":3341,"end":3346},"obj":"0.998461,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"97"},{"span":{"begin":3347,"end":3359},"obj":"0.9965588,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"98"},{"span":{"begin":3370,"end":3403},"obj":"0.99343634,structure_element,cleaner0,2023-07-05T08:51:32Z,SO:","id":"99"},{"span":{"begin":3421,"end":3444},"obj":"0.96191806,structure_element,cleaner0,2023-07-05T08:51:36Z,SO:","id":"100"},{"span":{"begin":3461,"end":3466},"obj":"0.6941337,structure_element,cleaner0,2023-07-05T08:51:44Z,SO:","id":"102"},{"span":{"begin":3479,"end":3491},"obj":"0.9979013,site,cleaner0,2023-07-05T08:51:58Z,SO:","id":"103"},{"span":{"begin":3496,"end":3498},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:01:22Z","id":"603"},{"span":{"begin":3498,"end":3502},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:52:54Z","id":"604"},{"span":{"begin":3518,"end":3520},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:01:47Z","id":"605"},{"span":{"begin":3520,"end":3524},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:52:47Z","id":"606"},{"span":{"begin":3544,"end":3565},"obj":"0.9527997,protein_state,cleaner0,2023-07-05T08:53:22Z,DUMMY:","id":"106"},{"span":{"begin":3602,"end":3611},"obj":"0.99544466,structure_element,cleaner0,2023-07-05T08:51:48Z,SO:","id":"107"},{"span":{"begin":3673,"end":3678},"obj":"chemical,CHEBI:,melaniev@ebi.ac.uk,2023-07-21T12:02:44Z","id":"731"},{"span":{"begin":3688,"end":3702},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"705"},{"span":{"begin":3709,"end":3720},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"730"},{"span":{"begin":3774,"end":3788},"obj":"0.9968951,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"108"},{"span":{"begin":3841,"end":3853},"obj":"0.884992,protein_state,cleaner0,2023-07-04T16:22:07Z,DUMMY:","id":"109"},{"span":{"begin":3854,"end":3860},"obj":"0.98747534,residue_name,cleaner0,2023-07-05T08:02:11Z,SO:","id":"110"},{"span":{"begin":3903,"end":3907},"obj":"0.99885833,ptm,melaniev@ebi.ac.uk,2023-07-21T11:52:08Z,MESH:","id":"112"},{"span":{"begin":3952,"end":3962},"obj":"0.9932809,structure_element,cleaner0,2023-07-05T08:52:02Z,SO:","id":"114"},{"span":{"begin":4055,"end":4063},"obj":"chemical,CHEBI:,melaniev@ebi.ac.uk,2023-07-21T11:51:04Z","id":"721"},{"span":{"begin":4090,"end":4095},"obj":"0.99896455,residue_name_number,cleaner0,2023-07-05T08:02:27Z,DUMMY:","id":"115"},{"span":{"begin":4100,"end":4105},"obj":"0.99897707,residue_name_number,cleaner0,2023-07-05T08:02:31Z,DUMMY:","id":"116"},{"span":{"begin":4228,"end":4236},"obj":"chemical,CHEBI:,melaniev@ebi.ac.uk,2023-07-21T11:51:04Z","id":"722"},{"span":{"begin":4295,"end":4309},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"716"},{"span":{"begin":4465,"end":4470},"obj":"0.99895763,residue_name_number,cleaner0,2023-07-05T08:02:27Z,DUMMY:","id":"117"},{"span":{"begin":4537,"end":4547},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"720"},{"span":{"begin":4621,"end":4631},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"719"},{"span":{"begin":4709,"end":4714},"obj":"0.9987826,residue_name_number,cleaner0,2023-07-05T08:02:27Z,DUMMY:","id":"118"},{"span":{"begin":4795,"end":4803},"obj":"chemical,CHEBI:,melaniev@ebi.ac.uk,2023-07-21T11:51:04Z","id":"723"},{"span":{"begin":4847,"end":4861},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"707"},{"span":{"begin":4867,"end":4875},"obj":"chemical,CHEBI:,melaniev@ebi.ac.uk,2023-07-21T11:51:04Z","id":"724"},{"span":{"begin":4908,"end":4922},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"704"},{"span":{"begin":4927,"end":4953},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"706"},{"span":{"begin":4959,"end":4965},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"709"},{"span":{"begin":4985,"end":4993},"obj":"chemical,CHEBI:,melaniev@ebi.ac.uk,2023-07-21T11:51:04Z","id":"725"},{"span":{"begin":5223,"end":5245},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"711"},{"span":{"begin":5271,"end":5296},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"710"},{"span":{"begin":5333,"end":5338},"obj":"0.9991684,residue_name_number,cleaner0,2023-07-05T08:02:41Z,DUMMY:","id":"119"},{"span":{"begin":5368,"end":5373},"obj":"0.9991742,residue_name_number,cleaner0,2023-07-05T08:02:45Z,DUMMY:","id":"120"},{"span":{"begin":5411,"end":5416},"obj":"0.9991697,residue_name_number,cleaner0,2023-07-05T08:02:44Z,DUMMY:","id":"121"},{"span":{"begin":5440,"end":5453},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"713"},{"span":{"begin":5485,"end":5489},"obj":"0.9990522,ptm,melaniev@ebi.ac.uk,2023-07-21T11:52:08Z,MESH:","id":"122"},{"span":{"begin":5538,"end":5543},"obj":"0.99915934,residue_name_number,cleaner0,2023-07-05T08:02:45Z,DUMMY:","id":"123"},{"span":{"begin":5621,"end":5625},"obj":"0.9990495,ptm,melaniev@ebi.ac.uk,2023-07-21T11:52:08Z,MESH:","id":"124"},{"span":{"begin":5649,"end":5662},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"714"},{"span":{"begin":5686,"end":5691},"obj":"0.99916136,residue_name_number,cleaner0,2023-07-05T08:02:52Z,DUMMY:","id":"125"},{"span":{"begin":5716,"end":5720},"obj":"0.9988856,ptm,melaniev@ebi.ac.uk,2023-07-21T11:52:08Z,MESH:","id":"126"},{"span":{"begin":5738,"end":5751},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"712"},{"span":{"begin":5816,"end":5821},"obj":"0.9991516,residue_name_number,cleaner0,2023-07-05T08:02:27Z,DUMMY:","id":"127"},{"span":{"begin":5836,"end":5841},"obj":"0.9917144,chemical,cleaner0,2023-07-05T08:55:01Z,CHEBI:","id":"128"},{"span":{"begin":5851,"end":5864},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"715"},{"span":{"begin":5901,"end":5906},"obj":"0.99916196,residue_name_number,cleaner0,2023-07-05T08:02:57Z,DUMMY:","id":"129"},{"span":{"begin":5981,"end":5986},"obj":"0.9983511,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"130"},{"span":{"begin":5987,"end":6017},"obj":"0.9934926,site,cleaner0,2023-07-05T08:03:03Z,SO:","id":"131"},{"span":{"begin":6036,"end":6076},"obj":"0.9922565,experimental_method,cleaner0,2023-07-05T08:03:06Z,MESH:","id":"132"},{"span":{"begin":6149,"end":6154},"obj":"0.99884135,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"133"},{"span":{"begin":6155,"end":6167},"obj":"0.94870484,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"134"},{"span":{"begin":6171,"end":6173},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:03:24Z","id":"607"},{"span":{"begin":6173,"end":6177},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:54:19Z","id":"608"},{"span":{"begin":6193,"end":6214},"obj":"0.995806,evidence,cleaner0,2023-07-05T08:03:41Z,DUMMY:","id":"136"},{"span":{"begin":6216,"end":6218},"obj":"0.9937781,evidence,cleaner0,2023-07-05T08:03:45Z,DUMMY:","id":"137"},{"span":{"begin":6228,"end":6250},"obj":"0.9887676,complex_assembly,cleaner0,2023-07-05T08:35:55Z,GO:","id":"138"},{"span":{"begin":6298,"end":6323},"obj":"0.9937454,experimental_method,cleaner0,2023-07-05T08:04:07Z,MESH:","id":"139"},{"span":{"begin":6379,"end":6397},"obj":"0.99432206,evidence,cleaner0,2023-07-05T08:04:01Z,DUMMY:","id":"140"},{"span":{"begin":6497,"end":6499},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:04:40Z","id":"609"},{"span":{"begin":6499,"end":6503},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:54:27Z","id":"610"},{"span":{"begin":6519,"end":6524},"obj":"0.9988524,protein,cleaner0,2023-07-04T16:20:21Z,PR:","id":"143"},{"span":{"begin":6548,"end":6550},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:08:27Z","id":"611"},{"span":{"begin":6550,"end":6554},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:54:36Z","id":"612"},{"span":{"begin":6569,"end":6574},"obj":"0.99658173,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"145"},{"span":{"begin":6589,"end":6608},"obj":"0.8414014,experimental_method,cleaner0,2023-07-05T08:57:36Z,MESH:","id":"146"},{"span":{"begin":6638,"end":6643},"obj":"0.9963198,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"147"},{"span":{"begin":6672,"end":6693},"obj":"0.9293416,experimental_method,cleaner0,2023-07-05T08:57:39Z,MESH:","id":"148"},{"span":{"begin":6728,"end":6730},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:09:10Z","id":"613"},{"span":{"begin":6730,"end":6734},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:54:53Z","id":"614"},{"span":{"begin":6736,"end":6738},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:09:38Z","id":"615"},{"span":{"begin":6738,"end":6742},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:55:01Z","id":"616"},{"span":{"begin":6747,"end":6749},"obj":"0.7814144,protein_type,cleaner0,2023-07-05T07:55:54Z,MESH:","id":"151"},{"span":{"begin":6817,"end":6819},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:10:08Z","id":"617"},{"span":{"begin":6819,"end":6823},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:54:45Z","id":"618"},{"span":{"begin":6828,"end":6830},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:10:36Z","id":"619"},{"span":{"begin":6830,"end":6834},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:55:10Z","id":"620"},{"span":{"begin":6852,"end":6857},"obj":"0.99671257,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"154"},{"span":{"begin":6858,"end":6866},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:57:52Z","id":"690"},{"span":{"begin":6914,"end":6916},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:38:01Z","id":"668"},{"span":{"begin":6916,"end":6920},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:55:18Z","id":"669"},{"span":{"begin":6934,"end":6939},"obj":"0.9966935,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"156"},{"span":{"begin":6958,"end":6960},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:38:30Z","id":"670"},{"span":{"begin":6960,"end":6964},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:55:26Z","id":"671"},{"span":{"begin":6996,"end":7022},"obj":"0.99616396,protein_type,cleaner0,2023-07-05T08:06:46Z,MESH:","id":"158"},{"span":{"begin":7024,"end":7028},"obj":"0.9961572,protein_type,cleaner0,2023-07-05T08:06:50Z,MESH:","id":"159"},{"span":{"begin":7034,"end":7054},"obj":"0.99562824,protein_type,cleaner0,2023-07-05T08:07:02Z,MESH:","id":"160"},{"span":{"begin":7056,"end":7061},"obj":"0.9862266,protein_type,cleaner0,2023-07-05T08:07:06Z,MESH:","id":"161"},{"span":{"begin":7114,"end":7119},"obj":"0.9961592,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"163"},{"span":{"begin":7141,"end":7146},"obj":"0.99671113,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"164"},{"span":{"begin":7147,"end":7151},"obj":"0.9969458,protein_type,cleaner0,2023-07-05T08:06:51Z,MESH:","id":"165"},{"span":{"begin":7153,"end":7157},"obj":"0.99758315,protein,cleaner0,2023-07-05T08:07:12Z,PR:","id":"166"},{"span":{"begin":7159,"end":7163},"obj":"0.9978067,protein,cleaner0,2023-07-05T08:07:16Z,PR:","id":"167"},{"span":{"begin":7169,"end":7175},"obj":"0.9977192,protein,cleaner0,2023-07-05T08:07:20Z,PR:","id":"168"},{"span":{"begin":7180,"end":7185},"obj":"0.9930031,protein_type,cleaner0,2023-07-05T08:07:06Z,MESH:","id":"169"},{"span":{"begin":7187,"end":7191},"obj":"0.99792385,protein,cleaner0,2023-07-05T08:07:24Z,PR:","id":"170"},{"span":{"begin":7193,"end":7197},"obj":"0.99804014,protein,cleaner0,2023-07-05T08:07:27Z,PR:","id":"171"},{"span":{"begin":7203,"end":7207},"obj":"0.9978777,protein,cleaner0,2023-07-05T08:07:31Z,PR:","id":"172"},{"span":{"begin":7214,"end":7221},"obj":"0.53316224,experimental_method,cleaner0,2023-07-05T09:00:08Z,MESH:","id":"173"},{"span":{"begin":7275,"end":7277},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:11:11Z","id":"621"},{"span":{"begin":7277,"end":7281},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:55:34Z","id":"622"},{"span":{"begin":7335,"end":7338},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:58:28Z","id":"691"},{"span":{"begin":7339,"end":7347},"obj":"0.47926757,experimental_method,cleaner0,2023-07-05T09:00:12Z,MESH:","id":"175"},{"span":{"begin":7405,"end":7409},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:58:22Z","id":"692"},{"span":{"begin":7410,"end":7418},"obj":"experimental_method,MESH:,cleaner0,2023-07-05T09:04:29Z","id":"695"},{"span":{"begin":7461,"end":7463},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:11:41Z","id":"623"},{"span":{"begin":7463,"end":7467},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:55:48Z","id":"624"},{"span":{"begin":7536,"end":7538},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:12:21Z","id":"625"},{"span":{"begin":7538,"end":7542},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:55:41Z","id":"626"},{"span":{"begin":7587,"end":7589},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:12:47Z","id":"627"},{"span":{"begin":7589,"end":7593},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:55:56Z","id":"628"},{"span":{"begin":7628,"end":7633},"obj":"0.9963509,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"179"},{"span":{"begin":7725,"end":7729},"obj":"0.9969043,protein_type,cleaner0,2023-07-05T08:06:51Z,MESH:","id":"180"},{"span":{"begin":7734,"end":7739},"obj":"0.9925954,protein_type,cleaner0,2023-07-05T08:07:06Z,MESH:","id":"181"},{"span":{"begin":7777,"end":7787},"obj":"protein_state,DUMMY:,cleaner0,2023-07-04T16:22:11Z","id":"584"},{"span":{"begin":7788,"end":7795},"obj":"protein_type,MESH:,cleaner0,2023-07-04T16:21:00Z","id":"565"},{"span":{"begin":7807,"end":7812},"obj":"0.9988348,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"182"},{"span":{"begin":7813,"end":7825},"obj":"0.9854789,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"183"},{"span":{"begin":7834,"end":7844},"obj":"0.9957682,protein_state,cleaner0,2023-07-04T16:22:11Z,DUMMY:","id":"184"},{"span":{"begin":7845,"end":7847},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:13:59Z","id":"630"},{"span":{"begin":7847,"end":7849},"obj":"residue_name_number,DUMMY:,cleaner0,2023-07-05T08:14:10Z","id":"631"},{"span":{"begin":7904,"end":7906},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:14:26Z","id":"632"},{"span":{"begin":7906,"end":7910},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:56:09Z","id":"633"},{"span":{"begin":7939,"end":7944},"obj":"0.99873716,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"187"},{"span":{"begin":7953,"end":7967},"obj":"0.9983891,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"188"},{"span":{"begin":7989,"end":8000},"obj":"0.9863785,experimental_method,cleaner0,2023-07-05T08:18:57Z,MESH:","id":"189"},{"span":{"begin":8030,"end":8040},"obj":"0.990856,chemical,cleaner0,2023-07-05T08:36:15Z,CHEBI:","id":"190"},{"span":{"begin":8044,"end":8054},"obj":"0.9934884,chemical,cleaner0,2023-07-05T08:38:55Z,CHEBI:","id":"191"},{"span":{"begin":8067,"end":8075},"obj":"0.96406466,experimental_method,cleaner0,2023-07-05T09:00:19Z,MESH:","id":"193"},{"span":{"begin":8085,"end":8096},"obj":"protein_state,DUMMY:,cleaner0,2023-07-05T08:53:55Z","id":"688"},{"span":{"begin":8097,"end":8102},"obj":"0.9987318,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"195"},{"span":{"begin":8103,"end":8115},"obj":"0.98387945,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"196"},{"span":{"begin":8167,"end":8169},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:15:14Z","id":"636"},{"span":{"begin":8169,"end":8173},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:56:22Z","id":"637"},{"span":{"begin":8182,"end":8199},"obj":"evidence,DUMMY:,cleaner0,2023-07-05T08:59:29Z","id":"694"},{"span":{"begin":8231,"end":8234},"obj":"experimental_method,MESH:,cleaner0,2023-07-05T09:04:29Z","id":"693"},{"span":{"begin":8305,"end":8307},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:15:40Z","id":"638"},{"span":{"begin":8307,"end":8311},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:56:29Z","id":"639"},{"span":{"begin":8412,"end":8422},"obj":"0.49922895,evidence,cleaner0,2023-07-05T08:56:27Z,DUMMY:","id":"199"},{"span":{"begin":8426,"end":8431},"obj":"0.99908006,residue_name_number,cleaner0,2023-07-05T08:15:58Z,DUMMY:","id":"200"},{"span":{"begin":8436,"end":8441},"obj":"0.9990513,residue_name_number,cleaner0,2023-07-05T08:02:27Z,DUMMY:","id":"201"},{"span":{"begin":8449,"end":8461},"obj":"0.98532,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"202"},{"span":{"begin":8489,"end":8491},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:16:15Z","id":"640"},{"span":{"begin":8491,"end":8495},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:56:52Z","id":"641"},{"span":{"begin":8500,"end":8502},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:16:48Z","id":"642"},{"span":{"begin":8502,"end":8506},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:56:37Z","id":"643"},{"span":{"begin":8570,"end":8617},"obj":"site,SO:,cleaner0,2023-07-05T08:13:40Z","id":"629"},{"span":{"begin":8684,"end":8689},"obj":"0.998936,residue_name_number,cleaner0,2023-07-05T08:02:27Z,DUMMY:","id":"207"},{"span":{"begin":8747,"end":8749},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:17:15Z","id":"644"},{"span":{"begin":8749,"end":8753},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:57:01Z","id":"645"},{"span":{"begin":8774,"end":8776},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:17:45Z","id":"646"},{"span":{"begin":8776,"end":8780},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:56:45Z","id":"647"},{"span":{"begin":8953,"end":8965},"obj":"0.99369735,complex_assembly,cleaner0,2023-07-05T08:18:01Z,GO:","id":"210"},{"span":{"begin":9001,"end":9006},"obj":"0.99862266,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"211"},{"span":{"begin":9007,"end":9019},"obj":"0.9849653,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"212"},{"span":{"begin":9067,"end":9077},"obj":"residue_name,SO:,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z","id":"696"},{"span":{"begin":9098,"end":9123},"obj":"0.99509495,experimental_method,cleaner0,2023-07-05T09:00:34Z,MESH:","id":"213"},{"span":{"begin":9130,"end":9132},"obj":"0.99270695,protein_type,cleaner0,2023-07-05T07:55:54Z,MESH:","id":"214"},{"span":{"begin":9142,"end":9152},"obj":"0.9932382,protein_state,cleaner0,2023-07-04T16:22:11Z,DUMMY:","id":"216"},{"span":{"begin":9154,"end":9167},"obj":"0.956428,protein_state,cleaner0,2023-07-05T08:40:11Z,DUMMY:","id":"217"},{"span":{"begin":9169,"end":9180},"obj":"0.9795297,protein_state,cleaner0,2023-07-05T08:40:15Z,DUMMY:","id":"218"},{"span":{"begin":9186,"end":9198},"obj":"0.97335297,protein_state,cleaner0,2023-07-04T16:22:07Z,DUMMY:","id":"219"},{"span":{"begin":9202,"end":9210},"obj":"residue_name_number,DUMMY:,cleaner0,2023-07-05T08:18:20Z","id":"648"},{"span":{"begin":9221,"end":9225},"obj":"0.9283707,residue_range,cleaner0,2023-07-05T08:50:16Z,DUMMY:","id":"222"},{"span":{"begin":9229,"end":9231},"obj":"0.951781,protein_type,cleaner0,2023-07-05T07:55:54Z,MESH:","id":"223"},{"span":{"begin":9287,"end":9292},"obj":"0.99854577,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"224"},{"span":{"begin":9293,"end":9305},"obj":"0.98509496,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"225"},{"span":{"begin":9329,"end":9339},"obj":"chemical,CHEBI:,cleaner0,2023-07-05T08:33:09Z","id":"649"},{"span":{"begin":9362,"end":9370},"obj":"0.78338593,protein_state,cleaner0,2023-07-05T08:54:04Z,DUMMY:","id":"228"},{"span":{"begin":9408,"end":9410},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:20:37Z","id":"653"},{"span":{"begin":9410,"end":9414},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:57:16Z","id":"654"},{"span":{"begin":9420,"end":9422},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:21:11Z","id":"655"},{"span":{"begin":9422,"end":9426},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:57:35Z","id":"656"},{"span":{"begin":9428,"end":9430},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:21:37Z","id":"657"},{"span":{"begin":9430,"end":9434},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:57:44Z","id":"658"},{"span":{"begin":9439,"end":9441},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:22:10Z","id":"659"},{"span":{"begin":9441,"end":9445},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:57:54Z","id":"660"},{"span":{"begin":9463,"end":9496},"obj":"0.98849183,experimental_method,cleaner0,2023-07-05T08:19:00Z,MESH:","id":"234"},{"span":{"begin":9510,"end":9520},"obj":"chemical,CHEBI:,cleaner0,2023-07-05T08:33:21Z","id":"650"},{"span":{"begin":9522,"end":9532},"obj":"chemical,CHEBI:,cleaner0,2023-07-05T08:33:34Z","id":"651"},{"span":{"begin":9538,"end":9548},"obj":"chemical,CHEBI:,cleaner0,2023-07-05T08:33:45Z","id":"652"},{"span":{"begin":9565,"end":9593},"obj":"evidence,DUMMY:,cleaner0,2023-07-05T09:01:01Z","id":"697"},{"span":{"begin":9601,"end":9606},"obj":"0.9984143,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"241"},{"span":{"begin":9607,"end":9619},"obj":"0.9821952,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"242"},{"span":{"begin":9734,"end":9744},"obj":"chemical,CHEBI:,cleaner0,2023-07-05T08:33:09Z","id":"663"},{"span":{"begin":9796,"end":9798},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:22:49Z","id":"661"},{"span":{"begin":9798,"end":9802},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:58:04Z","id":"662"},{"span":{"begin":9848,"end":9879},"obj":"0.99294585,experimental_method,cleaner0,2023-07-05T09:01:12Z,MESH:","id":"246"},{"span":{"begin":9904,"end":9909},"obj":"0.9990103,residue_name_number,cleaner0,2023-07-05T08:15:59Z,DUMMY:","id":"248"},{"span":{"begin":9986,"end":10000},"obj":"0.9981839,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"249"},{"span":{"begin":10125,"end":10133},"obj":"chemical,CHEBI:,melaniev@ebi.ac.uk,2023-07-21T11:51:04Z","id":"726"},{"span":{"begin":10145,"end":10152},"obj":"0.99031365,protein_state,cleaner0,2023-07-05T08:49:33Z,DUMMY:","id":"252"},{"span":{"begin":10153,"end":10158},"obj":"0.9989976,residue_name_number,cleaner0,2023-07-05T08:15:59Z,DUMMY:","id":"253"},{"span":{"begin":10195,"end":10205},"obj":"protein_state,DUMMY:,cleaner0,2023-07-05T09:01:51Z","id":"698"},{"span":{"begin":10206,"end":10211},"obj":"0.9989625,residue_name_number,cleaner0,2023-07-05T08:15:59Z,DUMMY:","id":"254"},{"span":{"begin":10257,"end":10265},"obj":"0.885494,protein_state,cleaner0,2023-07-05T08:54:04Z,DUMMY:","id":"255"},{"span":{"begin":10291,"end":10296},"obj":"0.9990196,residue_name_number,cleaner0,2023-07-05T08:15:59Z,DUMMY:","id":"257"},{"span":{"begin":10354,"end":10362},"obj":"0.9797934,experimental_method,cleaner0,2023-07-05T09:01:59Z,MESH:","id":"258"},{"span":{"begin":10366,"end":10371},"obj":"0.99903935,residue_name_number,cleaner0,2023-07-05T08:24:25Z,DUMMY:","id":"259"},{"span":{"begin":10410,"end":10415},"obj":"0.9990657,residue_name_number,cleaner0,2023-07-05T08:02:27Z,DUMMY:","id":"260"},{"span":{"begin":10515,"end":10529},"obj":"0.99843556,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"261"},{"span":{"begin":10533,"end":10542},"obj":"0.984743,protein_state,cleaner0,2023-07-05T08:54:12Z,DUMMY:","id":"262"},{"span":{"begin":10554,"end":10559},"obj":"0.99253696,species,cleaner0,2023-07-04T16:22:25Z,MESH:","id":"263"},{"span":{"begin":10560,"end":10573},"obj":"structure_element,SO:,cleaner0,2023-07-05T08:49:39Z","id":"684"},{"span":{"begin":10577,"end":10598},"obj":"0.9765474,experimental_method,cleaner0,2023-07-05T09:02:03Z,MESH:","id":"265"},{"span":{"begin":10625,"end":10635},"obj":"0.9461614,protein_state,cleaner0,2023-07-04T16:22:11Z,DUMMY:","id":"267"},{"span":{"begin":10637,"end":10650},"obj":"0.9879154,protein_state,cleaner0,2023-07-05T08:40:11Z,DUMMY:","id":"268"},{"span":{"begin":10652,"end":10663},"obj":"0.9869178,protein_state,cleaner0,2023-07-05T08:40:15Z,DUMMY:","id":"269"},{"span":{"begin":10669,"end":10681},"obj":"0.9762997,protein_state,cleaner0,2023-07-04T16:22:07Z,DUMMY:","id":"270"},{"span":{"begin":10682,"end":10689},"obj":"protein_type,MESH:,cleaner0,2023-07-05T09:02:17Z","id":"699"},{"span":{"begin":10741,"end":10754},"obj":"structure_element,SO:,cleaner0,2023-07-05T08:49:39Z","id":"685"},{"span":{"begin":10788,"end":10802},"obj":"residue_name,SO:,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z","id":"544"},{"span":{"begin":10883,"end":10889},"obj":"0.9987778,protein,cleaner0,2023-07-05T08:39:48Z,PR:","id":"275"},{"span":{"begin":10894,"end":10897},"obj":"0.99860966,protein,cleaner0,2023-07-05T07:54:09Z,PR:","id":"276"},{"span":{"begin":10925,"end":10937},"obj":"0.9837325,protein_state,cleaner0,2023-07-04T16:22:07Z,DUMMY:","id":"277"},{"span":{"begin":10948,"end":10953},"obj":"0.99857676,protein,cleaner0,2023-07-05T08:39:56Z,PR:","id":"279"},{"span":{"begin":10958,"end":10961},"obj":"0.9983223,protein,cleaner0,2023-07-05T07:54:15Z,PR:","id":"280"},{"span":{"begin":10968,"end":10976},"obj":"0.99105185,protein_state,cleaner0,2023-07-05T08:54:04Z,DUMMY:","id":"281"},{"span":{"begin":11018,"end":11030},"obj":"0.9855747,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"283"},{"span":{"begin":11040,"end":11059},"obj":"0.80789137,protein_type,cleaner0,2023-07-05T08:52:52Z,MESH:","id":"284"},{"span":{"begin":11061,"end":11072},"obj":"0.9922646,structure_element,cleaner0,2023-07-05T08:52:07Z,SO:","id":"285"},{"span":{"begin":11093,"end":11107},"obj":"0.99855334,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"286"},{"span":{"begin":11135,"end":11138},"obj":"0.7588632,structure_element,cleaner0,2023-07-04T16:21:53Z,SO:","id":"287"},{"span":{"begin":11142,"end":11163},"obj":"0.9541701,experimental_method,cleaner0,2023-07-05T09:02:34Z,MESH:","id":"288"},{"span":{"begin":11214,"end":11226},"obj":"0.99803704,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"289"},{"span":{"begin":11231,"end":11246},"obj":"0.9968952,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"290"},{"span":{"begin":11300,"end":11312},"obj":"0.9787652,structure_element,cleaner0,2023-07-04T16:21:48Z,SO:","id":"291"},{"span":{"begin":11400,"end":11414},"obj":"0.99844176,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"292"},{"span":{"begin":11434,"end":11437},"obj":"0.8739639,structure_element,cleaner0,2023-07-04T16:21:53Z,SO:","id":"293"},{"span":{"begin":11441,"end":11445},"obj":"0.99858606,protein,cleaner0,2023-07-05T08:51:13Z,PR:","id":"294"},{"span":{"begin":11450,"end":11454},"obj":"0.9986286,protein,cleaner0,2023-07-05T08:51:16Z,PR:","id":"295"},{"span":{"begin":11518,"end":11530},"obj":"0.98622835,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"296"},{"span":{"begin":11563,"end":11577},"obj":"0.9985879,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"297"},{"span":{"begin":11617,"end":11629},"obj":"0.99071395,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"298"},{"span":{"begin":11633,"end":11638},"obj":"0.9987459,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"299"},{"span":{"begin":11662,"end":11669},"obj":"0.5421235,protein_type,cleaner0,2023-07-04T16:21:00Z,MESH:","id":"300"},{"span":{"begin":11670,"end":11683},"obj":"0.672082,ptm,cleaner0,2023-07-04T16:18:43Z,MESH:","id":"301"},{"span":{"begin":11756,"end":11770},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"718"},{"span":{"begin":11825,"end":11833},"obj":"chemical,CHEBI:,melaniev@ebi.ac.uk,2023-07-21T11:51:04Z","id":"727"},{"span":{"begin":11870,"end":11872},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:41:07Z","id":"672"},{"span":{"begin":11872,"end":11876},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T12:01:20Z","id":"673"},{"span":{"begin":11887,"end":11892},"obj":"0.99646616,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"303"},{"span":{"begin":11925,"end":11929},"obj":"0.9973616,protein_type,cleaner0,2023-07-05T08:06:51Z,MESH:","id":"304"},{"span":{"begin":11934,"end":11939},"obj":"0.9948607,protein_type,cleaner0,2023-07-05T08:07:06Z,MESH:","id":"305"},{"span":{"begin":11983,"end":11993},"obj":"residue_name,SO:,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z","id":"700"},{"span":{"begin":12009,"end":12014},"obj":"0.998776,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"306"},{"span":{"begin":12015,"end":12027},"obj":"0.9936651,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"307"},{"span":{"begin":12151,"end":12165},"obj":"residue_name,SO:,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z","id":"545"},{"span":{"begin":12217,"end":12222},"obj":"0.9987233,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"308"},{"span":{"begin":12250,"end":12264},"obj":"0.99826485,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"309"},{"span":{"begin":12269,"end":12281},"obj":"0.9959139,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"310"},{"span":{"begin":12341,"end":12355},"obj":"residue_name,SO:,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z","id":"546"},{"span":{"begin":12377,"end":12382},"obj":"0.9981281,protein_type,cleaner0,2023-07-05T08:52:37Z,MESH:","id":"311"},{"span":{"begin":20558,"end":20560},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:46:18Z","id":"674"},{"span":{"begin":20560,"end":20564},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:59:06Z","id":"675"},{"span":{"begin":20591,"end":20605},"obj":"0.99838877,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"502"},{"span":{"begin":20615,"end":20632},"obj":"0.99736893,evidence,cleaner0,2023-07-05T08:56:31Z,DUMMY:","id":"503"},{"span":{"begin":20640,"end":20645},"obj":"0.99835616,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"504"},{"span":{"begin":20646,"end":20658},"obj":"0.97807664,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"505"},{"span":{"begin":20667,"end":20682},"obj":"protein_state,DUMMY:,cleaner0,2023-07-05T08:54:40Z","id":"689"},{"span":{"begin":20687,"end":20697},"obj":"0.80304146,chemical,cleaner0,2023-07-05T08:36:15Z,CHEBI:","id":"507"},{"span":{"begin":20719,"end":20721},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:46:58Z","id":"676"},{"span":{"begin":20721,"end":20725},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:58:57Z","id":"677"},{"span":{"begin":20783,"end":20819},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"728"},{"span":{"begin":20829,"end":20834},"obj":"0.99865216,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"510"},{"span":{"begin":20835,"end":20847},"obj":"0.9790957,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"511"},{"span":{"begin":20857,"end":20871},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:20:44Z","id":"708"},{"span":{"begin":20913,"end":20927},"obj":"0.9983652,residue_name,melaniev@ebi.ac.uk,2023-07-06T15:25:20Z,SO:","id":"512"},{"span":{"begin":20932,"end":20934},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:47:40Z","id":"678"},{"span":{"begin":20934,"end":20938},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:59:33Z","id":"679"},{"span":{"begin":20968,"end":20973},"obj":"0.9988475,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"514"},{"span":{"begin":20974,"end":20986},"obj":"0.9892417,structure_element,cleaner0,2023-07-04T16:20:28Z,SO:","id":"515"},{"span":{"begin":20994,"end":21006},"obj":"0.98307806,experimental_method,cleaner0,2023-07-05T09:03:32Z,MESH:","id":"516"},{"span":{"begin":21040,"end":21042},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:48:14Z","id":"680"},{"span":{"begin":21042,"end":21046},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T11:59:41Z","id":"681"},{"span":{"begin":21051,"end":21053},"obj":"protein_type,MESH:,cleaner0,2023-07-05T08:48:42Z","id":"682"},{"span":{"begin":21053,"end":21057},"obj":"ptm,MESH:,melaniev@ebi.ac.uk,2023-07-21T12:00:02Z","id":"683"},{"span":{"begin":21061,"end":21070},"obj":"0.9924296,protein_state,cleaner0,2023-07-05T08:49:13Z,DUMMY:","id":"519"},{"span":{"begin":21072,"end":21074},"obj":"0.98962665,protein_state,cleaner0,2023-07-05T08:49:18Z,DUMMY:","id":"520"},{"span":{"begin":21077,"end":21080},"obj":"protein_type,MESH:,melaniev@ebi.ac.uk,2023-07-21T12:00:29Z","id":"729"},{"span":{"begin":21094,"end":21098},"obj":"protein_type,MESH:,cleaner0,2023-07-05T09:03:46Z","id":"701"},{"span":{"begin":21099,"end":21107},"obj":"experimental_method,MESH:,cleaner0,2023-07-05T09:04:00Z","id":"702"},{"span":{"begin":21108,"end":21113},"obj":"0.99134904,taxonomy_domain,cleaner0,2023-07-04T16:22:20Z,DUMMY:","id":"521"},{"span":{"begin":21129,"end":21131},"obj":"0.9896226,protein_type,cleaner0,2023-07-05T07:55:54Z,MESH:","id":"522"},{"span":{"begin":21180,"end":21191},"obj":"0.90694416,experimental_method,cleaner0,2023-07-05T09:03:35Z,MESH:","id":"523"},{"span":{"begin":21192,"end":21199},"obj":"0.65750146,evidence,cleaner0,2023-07-05T08:57:05Z,DUMMY:","id":"524"},{"span":{"begin":21203,"end":21208},"obj":"0.9981918,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"525"},{"span":{"begin":21209,"end":21214},"obj":"0.99271107,structure_element,cleaner0,2023-07-05T08:52:13Z,SO:","id":"526"},{"span":{"begin":21227,"end":21237},"obj":"0.7894704,chemical,cleaner0,2023-07-05T08:36:15Z,CHEBI:","id":"527"},{"span":{"begin":21242,"end":21252},"obj":"chemical,CHEBI:,cleaner0,2023-07-05T08:38:55Z","id":"635"},{"span":{"begin":21267,"end":21275},"obj":"experimental_method,MESH:,cleaner0,2023-07-05T09:04:10Z","id":"703"},{"span":{"begin":21280,"end":21287},"obj":"0.6348235,evidence,cleaner0,2023-07-05T08:57:07Z,DUMMY:","id":"531"},{"span":{"begin":21354,"end":21366},"obj":"0.98869205,experimental_method,cleaner0,2023-07-05T08:49:22Z,MESH:","id":"532"},{"span":{"begin":21379,"end":21403},"obj":"0.99291915,experimental_method,cleaner0,2023-07-05T08:49:24Z,MESH:","id":"533"},{"span":{"begin":21410,"end":21419},"obj":"0.99699277,protein_state,cleaner0,2023-07-05T08:49:30Z,DUMMY:","id":"534"},{"span":{"begin":21424,"end":21431},"obj":"0.959159,protein_state,cleaner0,2023-07-05T08:49:33Z,DUMMY:","id":"535"},{"span":{"begin":21432,"end":21437},"obj":"0.9981369,protein,cleaner0,2023-07-04T16:20:22Z,PR:","id":"536"},{"span":{"begin":21438,"end":21451},"obj":"0.981699,structure_element,cleaner0,2023-07-05T08:49:39Z,SO:","id":"537"}],"relations":[]}]

annotated_BioC_JSON/PMC4888278_ann.json

@@ -0,0 +1 @@
+[{"sourceid":"4888278","sourcedb":"","project":"","target":"","text":"Structural determinant for inducing RORgamma specific inverse agonism triggered by a synthetic benzoxazinone ligand Background The nuclear hormone receptor RORγ regulates transcriptional genes involved in the production of the pro-inflammatory interleukin IL-17 which has been linked to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. This transcriptional activity of RORγ is modulated through a protein-protein interaction involving the activation function 2 (AF2) helix on the ligand binding domain of RORγ and a conserved LXXLL helix motif on coactivator proteins. Our goal was to develop a RORγ specific inverse agonist that would help down regulate pro-inflammatory gene transcription by disrupting the protein protein interaction with coactivator proteins as a therapeutic agent. Results We identified a novel series of synthetic benzoxazinone ligands having an agonist (BIO592) and inverse agonist (BIO399) mode of action in a FRET based assay. We show that the AF2 helix of RORγ is proteolytically sensitive when inverse agonist BIO399 binds. Using x-ray crystallography we show how small modifications on the benzoxazinone agonist BIO592 trigger inverse agonism of RORγ. Using an in vivo reporter assay, we show that the inverse agonist BIO399 displayed specificity for RORγ over ROR sub-family members α and β. Conclusion The synthetic benzoxazinone ligands identified in our FRET assay have an agonist (BIO592) or inverse agonist (BIO399) effect by stabilizing or destabilizing the agonist conformation of RORγ. The proteolytic sensitivity of the AF2 helix of RORγ demonstrates that it destabilizes upon BIO399 inverse agonist binding perturbing the coactivator protein binding site. Our structural investigation of the BIO592 agonist and BIO399 inverse agonist structures identified residue Met358 on RORγ as the trigger for RORγ specific inverse agonism. Electronic supplementary material The online version of this article (doi:10.1186/s12900-016-0059-3) contains supplementary material, which is available to authorized users. Background Retinoid-related orphan receptor gamma (RORγ) is a transcription factor belonging to a sub-family of nuclear receptors that includes two closely related members RORα and RORβ. Even though a high degree of sequence similarity exists between the RORs, their functional roles in regulation for physiological processes involved in development and immunity are distinct. During development, RORγ regulates the transcriptional genes involved in the functioning of multiple pro-inflammatory lymphocyte lineages including T helper cells (TH17cells) which are necessary for IL-17 production. IL-17 is a pro-inflammatory interleukin linked to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease; making its transcriptional regulation through RORγ an attractive therapeutic target. RORγ consists of an N-terminal DNA binding domain (DBD) connected to a C-terminal ligand binding domain (LBD) via a flexible hinge region. The DBD is composed of two zinc fingers that allow it to interact with specifically encoded regions on the DNA called the nuclear receptor response elements. The LBD consists of a coactivator protein binding pocket and a hydrophobic ligand binding site (LBS) which are responsible for regulating transcription. The coactivator binding pocket of RORγ recognizes a conserved helix motif LXXLL (where X can be any amino acid) on transcriptional coactivator complexes and recruits it to activate transcription. Like other nuclear hormone receptors, RORγ’s helix12 which makes up the C-termini of the LBD is an essential part of the coactivator binding pocket and is commonly referred to as the activation function helix 2 (AF2). In RORγ, the conformation of the AF2 helix required to form the coactivator binding pocket is mediated by a salt bridge between His479 and Tyr502 in addition to π- π interactions between Tyr502 and Phe506. The conformation of the AF2 helix can be modulated through targeted ligands which bind the LBS and increase the binding of the coactivator protein (agonists) or disrupt binding (inverse agonists) thereby enhancing or inhibiting transcription. Since RORγ has been demonstrated to play an important role in pro-inflammatory gene expression patterns implicated in several major autoimmune diseases, our aim was to develop RORγ inverse agonists that would help down regulate pro-inflammatory gene transcription. FRET results for agonist BIO592 (a) and Inverse Agonist BIO399 (b) Here we present the identification of two synthetic benzoxazinone RORγ ligands, a weak agonist BIO592 (Fig. 1a) and an inverse agonist BIO399 (Fig. 1b) which were identified using a Fluorescence Resonance Energy transfer (FRET) based assay that monitored coactivator peptide recruitment. Using partial proteolysis in combination with mass spectrometry analysis we demonstrate that the AF2 helix of RORγ destabilizes upon BIO399 (inverse agonist) binding. Finally, comparing binding modes of our benzoxazinone RORγ crystal structures to other ROR structures, we hypothesize a new mode of action for achieving inverse agonism and selectivity. Methods Cloning, protein expression and purification of RORγ518 GST-RORγ518 was constructed by sub-cloning residues 259 to 518 of a human RORγ cDNA into a pGEX-6P vector with a cleavable N-terminal GST fusion tag. BL21 (DE3) Escherichia coli cells were transformed with the plasmid encoding the GST-PreScission-hRORgamma 259–518 protein (GST-RORγ518) and were grown at 37 °C in LB media supplemented with ampicillin to an OD of 1. The temperature was reduced to 18 °C and protein expression was induced by adding 1 mM IPTG and was shaking for an additional 16 h. The cells were harvested and resuspended in lysis buffer (25 mM TRIS pH 8.0, 250 mM NaCl, 10 % Glycerol, 5 mM DTT and Roche EDTA-free protease inhibitor cocktail) and were lysed using a microfluidizer. The lysate was clarified by centrifugation at 20,000 × g for 1 h at 4 °C and GST-RORγ518 was captured by batch binding to Glutathione Sepharose resin overnight at 4 °C. The resin was washed with buffer A (25 mM TRIS pH 8.0, 250 mM NaCl, 10 % glycerol, 5 mM DTT) and loaded onto a XK column and washed until no non-specific unbound protein was detected. GST- RORγ518 was eluted from the column using buffer A supplemented with 10 mM Glutathione pH 8.0 and analyzed by SDS-PAGE. The eluate was then treated with PreScission Protease (10units/mg of protein) and further purified on a Superdex 75 column equilibrated in buffer B (25 mM TRIS pH 8.0, 250 mM NaCl, 5 % glycerol and 2 mM DTT). RORγ518 eluted as a monomer and was approximately 95 % pure as observed by SDS-PAGE. Additional constructs including c-terminal truncations, surface entropy reduction and cysteine scrubbed mutations were also expressed and purified in the same manner as RORγ518 if an expression level of \u003e1 mg/L was achieved. RORγ FRET based assay and GAL4 reporter assay FRET-based (Fluorescence Resonance Energy Transfer) assay and the GAL4 Reporter assay were performed as described previously. BIO592 and BIO399 were synthesized (Additional file 1) and belonged to a proprietary library where they were identified as RORγ activity modulators using the FRET-based assay. Partial proteolysis of RORγ518 RORγ518 at 8 mg/ml or in complex with 1 mM BIO399 or 1 mM BIO592 and 0.5 mM coactivator peptide EBI96 EFPYLLSLLGEVSPQ (New England Peptide) were treated with Actinase E (Hampton Research) added at a ratio of 1.25ugs of protease/1 mg of RORγ518 for 6 h at 4 °C. The reactions were quenched using 1X Protease inhibitor cocktail (Roche) + 1 mM EDTA and subjected to mass spectrometry analysis. Mass spectrometry of partially proteolyzed RORγ518 Proteolyzed RORγ518 samples were reduced with 50 mM dithiothreitol in 50 mM Tris pH 8.0, 150 mM NaCl containing 4 M urea and 5 mM EDTA. The sample was then analyzed on a LC-MS system comprised of a UPLC (ACQUITY, Waters Corp.), a TUV dual-wavelength UV detector (Waters Corp.), and a ZQ mass spectrometer (Waters Corp.). A Vydac C4 cartridge was used for desalting. Molecular masses for the Actinase E treated RORγ518 samples were obtained by deconvoluting the raw mass spectra using MaxLynx 4.1 software (Waters Corp.). Crystallization of RORγ518 with agonist BIO592 and inverse agonist BIO399 RORγ518 was concentrated to 8 mg/ml and EBI96 was added to a final concentration of 0.5 mM and agonist BIO592 to 1 mM and incubated on ice for 1 h. The coactivator peptide EBI96 which was identified by phage display was chosen for crystallization because of its strong interaction with RORγ in a mammalian two-hybrid analysis system that assessed the transactivation of RORγ. Diffraction quality crystals were grown through vapor diffusion in a buffer containing 0.1 M HEPES pH 8.0, 25 % PEG3350 and 0.2 M NaCl at 18 °C. Crystals were cryoprotected in the mother liquor containing 20 % glycerol as cryoprotectant prior to being frozen in liquid nitrogen for data collection. Actinase E proteolyzed RORγ518 BIO399 concentrated to 8 mg/ml was crystallized using vapor diffusion in a buffer containing 0.1 M BisTRIS pH 5.5, 0.2 M ammonium acetate and 15 % PEG3350 at 18 °C. Crystals were cryoprotected for data collection by transferring them to a mother liquor containing 15 % PEG400 prior to being frozen in liquid nitrogen. Data collection and structure determination for RORγ518 BIO592 and BIO399 complexes X-ray diffraction data for all the crystals were measured at beam line ID31 at the Argonne Photon Source. The data were processed with Mosflm in case of the RORγ518-BIO592-EBI96 ternary complex and with HKL2000 in the case of the Actinase E treated aeRORγ518/BIO399 complex. For both datasets, PDB ID: 3LOL was used as the search model, and the molecular replacement solutions were determined using MOLREP. The refinement was carried out using Refmac5 and model building was carried out in Coot. The data processing and refinement statistics are provided in Additional file 2. RORγ518-BIO592-EBI96 ternary complex: The data for the ternary complex were measured to 2.63 Å. It crystallized in a P21 space group with four molecules of the ternary complex in the asymmetric unit. The final model was refined to a Rcryst of 19.9 % and Rfree of 25.5 %. aeRORγ518/BIO399 complex: Diffraction data for the aeRORγ518-BIO399 complex were measured to 2.35 Å. It crystallized in C2 space group with two molecules in the asymmetric unit. The final model was refined to a Rcryst of 21.1 % and Rfree of 26.3 %. Results and discussion Identification of BIO592 and BIO399 as ligands that modulate RORγ coactivator peptide recruitment Using a FRET based assay we discovered agonist BIO592 (Fig. 1a) which increased the coactivator peptide TRAP220 recruitment to RORγ (EC50 0f 58nM and Emax of 130 %) and a potent inverse agonist BIO399 (Fig. 1b) which inhibited coactivator recruitment (IC50: 4.7nM). Interestingly, the structural difference between the agonist BIO592 and inverse agonist BIO399 was minor; with the 2,3-dihydrobenzo[1,4]oxazepin-4-one ring system of BIO399 being 3 atoms larger than the benzo[1,4]oxazine-3-one ring system of BIO592. In order to understand how small changes in the core ring system leads to inverse agonism, we wanted to structurally determine the binding mode of both BIO592 and BIO399 in the LBS of RORγ using x-ray crystallography. Structure of the RORγ518-BIO592-EBI96 ternary complex is in a transcriptionally active conformation \na The ternary structure of RORγ518 BIO592 and EBI96. b RORγ AF2 helix in the agonist conformation. c EBI96 coactivator peptide bound in the coactivator pocket of RORγ RORγ518 bound to agonist BIO592 was crystallized with a truncated form of the coactivator peptide EBI96 to a resolution of 2.6 Å (Fig. 2a). The structure of the ternary complex had features similar to other ROR agonist coactivator structures in a transcriptionally active canonical three layer helix fold with the AF2 helix in the agonist conformation. The agonist conformation is stabilized by a hydrogen bond between His479 and Tyr502, in addition to π-π interactions between His479, Tyr502 and Phe506 (Fig. 2b). The hydrogen bond between His479 and Tyr502 has been reported to be critical for RORγ agonist activity. Disrupting this interaction through mutagenesis reduced transcriptional activity of RORγ. This reduced transcriptional activity has been attributed to the inability of the AF2 helix to complete the formation of the coactivator binding pocket necessary for coactivator proteins to bind. Electron density for the coactivator peptide EBI96 was observed for residues EFPYLLSLLG which formed a α-helix stabilized through hydrophobic interactions with the coactivator binding pocket on RORγ (Fig. 2c). This interaction is further stabilized through a conserved charged clamp wherein the backbone amide of Tyr7 and carbonyl of Leu11 of EBI96 form hydrogen bonds with Glu504 (helix12) and Lys336 (helix3) of RORγ. Formation of this charged clamp is essential for RORγ’s function for playing a role in transcriptional activation and this has been corroborated through mutagenic studies in this region. BIO592 binds in a collapsed conformation stabilizing the agonist conformation of RORγ \na Collapsed binding mode of agonist BIO592 in the hydrophobic LBS of RORγ. b Benzoxazinone ring system of agonist BIO592 packing against His479 of RORγ stabilizing agonist conformation of the AF2 helix BIO592 bound in a collapsed conformational state in the LBS of RORγ with the xylene ring positioned at the bottom of the pocket making hydrophobic interactions with Val376, Phe378, Phe388 and Phe401, with the ethyl-benzoxazinone ring making several hydrophobic interactions with Trp317, Leu324, Met358, Leu391, Ile 400 and His479 (Fig. 3a, Additional file 3). The sulfonyl group faces the entrance of the pocket, while the CF3 makes a hydrophobic contact with Ala327. Hydrophobic interaction between the ethyl group of the benzoxazinone and His479 reinforce the His479 sidechain position for making the hydrogen bond with Tyr502 thereby stabilizing the agonist conformation (Fig. 3b). RORγ AF2 helix is sensitive to proteolysis in the presence of Inverse Agonist BIO399 Next, we attempted co-crystallization with the inverse agonist BIO399. However, extensive crystallization efforts with BIO399 and RORγ518 or other AF2 intact constructs did not produce crystals. We hypothesized that the RORγ518 coactivator peptide interaction in the FRET assay was disrupted upon BIO399 binding and that a conformational rearrangement of the AF2 helix could have occurred, hindering crystallization. Specific proteolytic positions on RORγ518 when treated with Actinase E alone (Green) or in the presence of BIO399 (Red) and shared proteolytic sites (Yellow) The unfolding of the AF2 helix has been observed for other nuclear hormone receptors when bound to an inverse agonist or antagonist. We used partial proteolysis in combination with mass spectrometry to determine if BIO399 was causing the AF2 helix to unfold. Results of the Actinase E proteolysis experiments on RORγ518, the ternary complex of RORγ518 with agonist BIO592 and coactivator EBI96, or in the presence of inverse agonist BIO399 supported our hypothesis. Analysis of the fragmentation pattern showed minimal proteolytic removal of the AF2 helix by Actinase E on RORγ518 alone (ending at 504 to 506) and the ternary complex remained primarily intact (ending at 515/518) (Additional file 4). However, in the presence of inverse agonist BIO399, the proteolytic pattern showed significantly less protection, albeit the products were more heterogeneous (majority ending at 494/495), indicating the destabilization of the AF2 helix compared to either the APO or ternary agonist complex (Fig. 4, Additional file 5). Several rounds of cocrystallization attempts with RORγ518 or other RORγ AF2 helix containing constructs complexed with BIO399 had not produced crystals. We attributed the inability to form crystals to the unfolding of the AF2 helix induced by BIO399. We reasoned that if we could remove the unfolded AF2 helix using proteolysis we could produce a binary complex more amenable to crystallization. AF2 truncated RORγ BIO399 complex is more amenable to crystallization \na The binary structure of AF2-truncated RORγ and BIO399. b The superposition of inverse agonist BIO399 (Cyan) and agonist BIO592 (Green). c Movement of Met358 and His479 in the BIO399 (Cyan) and BIO592 (Green) structures The Actinase E treated RORγ518 BIO399 ternary complex (aeRORγ493/4) co-crystallized readily in several PEG based conditions. The structure of aeRORγ493/4 BIO399 complex was solved to 2.3 Å and adopted a similar core fold to the BIO592 agonist crystal structure (Fig. 5a, Additional file 3). The aeRORγ493/4 BIO399 structure diverged at the c-terminal end of Helix 11 from the RORγ518 BIO592 EBI96 structure, where helix 11 unwinds into a random coil after residue L475. Inverse agonist BIO399 uses Met358 as a trigger for inverse agonism BIO399 binds to the ligand binding site of RORγ adopting a collapsed conformation as seen with BIO592 where the two compounds superimpose with an RMSD of 0.72 Å (Fig. 5b). The majority of the side chains within 4 Å of BIO399 and BIO592 adopt similar rotomer conformations with the exceptions of Met358 and His479 (Fig. 5c). The difference density map showed clear positive density for Met358 in an alternate rotomer conformation compared to the one observed in the molecular replacement model or the other agonist containing models (Additional file 6). We tried to refine Met358 in the same conformation as the molecular replacement model or the other agonist containing models, but the results clearly indicated that this was not possible, thus confirming the new rotamer conformation for the Met358 sidechain in the inverse agonist bound structure. The change in rotomer conformation of Met358 between the agonist and inverse agonist structures is attributed to the gem-dimethyl group on the larger 7 membered benzoxazinone ring system of BIO399. The comparison of the two structures shows that the agonist conformation observed in the BIO592 structure would be perturbed by BIO399 pushing Met358 into Phe506 of the AF2 helix indicating that Met358 is a trigger for inducing inverse agonism in RORγ (Fig. 5c). BIO399 and Inverse agonist T0901317 bind in a collapsed conformation distinct from other RORγ Inverse Agonists Cocrystal structures \na Overlay of RORγ structures bound to BIO596 (Green), BIO399 (Cyan) and T0901317 (Pink). b Overlay of M358 in RORγ structure BIO596 (Green), BIO399 (Cyan), Digoxin (Yellow), Compound 2 (Grey), Compound 48 (Salmon) and Compound 4j (Orange) The co-crystal structure of RORγ with T0901317 (PDB code: 4NB6), an inverse agonist of RORγ (IC50 of 54nM in an SRC1 displacement FRET assay and an IC50 of 59nM in our FRET assay (Additional file 7)) shows that it adopts a collapsed conformation similar to the structure of BIO399 described here. The two compounds superimpose with an RMSD of 0.81 Å (Fig. 6a). The CF3 group on the hexafluoropropanol group of T0901317 was reported to fit the electron density in two conformations one of which pushes Met358 into the vicinity of Phe506 in the RORγ BIO592 agonist structure. We hypothesize that since the Met358 sidechain conformation in the T0901317 RORγ structure is not in the BIO399 conformation, this difference could account for the 10-fold reduction in the inverse agonism for T0901317 compared to BIO399 in the FRET assay. Co-crystal structures of RORγ have been generated with several potent inverse agonists adopting a linear conformation distinct from the collapsed conformations seen for BIO399 and T090131718. The inverse agonist activity for these compounds has been attributed to orientating Trp317 to clash with Tyr502 or a direct inverse agonist hydrogen bonding event with His479, both of which would perturb the agonist conformation of RORγ. BIO399 neither orients the sidechain of Trp317 toward Tyr502 nor forms a hydrogen bond with His479 suggesting its mode of action is distinct from linear inverse agonists (Additional file 8). In the linear inverse agonist crystal structures the side chain of Met358 resides in a similar position as the rotomer observed in RORγ agonist structures with BIO592 described here or as observed in the hydroxycholesterol derivatives and therefore would not trigger inverse agonism with these ligands (Fig. 6b). BIO399 shows selectivity for RORγ over RORα and RORβ in a GAL4 Cellular Reporter Assay GAL4 cell assay selectivity profile for BIO399 toward RORα and RORβ in GAL4 ROR\tγ\tα\tβ\t \tIC50 (uM)\t0.043 (+/− 0.01uM; N = 6)\t\u003e10 (N = 2)\t\u003e1.2 (N = 2)\t \tSelectivity (X)\t-\t\u003e235\t\u003e28.2\t \t \na Overlay of RORα (yellow), β (pink) and γ (cyan) showing side chain differences at Met358 inverse agonism trigger position and (b) around the benzoxazinone ring system of BIO399 In order to assess the in vivo selectivity profile of BIO399 a cellular reporter assay was implemented where the ligand binding domains of ROR α, β and γ were fused to the DNA binding domain of the transcriptional factor GAL4. The ROR-GAL4 fusion proteins were expressed in cells with the luciferase reporter gene under the control of a GAL4 promoter. BIO399 inhibited the luciferase activity when added to the cells expressing the RORγ-GAL4 fusion with an in vivo IC50 of 42.5nM while showing \u003e235 and 28 fold selectivity over cells expressing GAL4 fused to the LBD of ROR α or β, respectively (Table 1). The LBS of RORs share a high degree of similarity. However, the inverse agonism trigger of BIO399, residue Met358, is a leucine in both RORα and β. This selectivity profile for BIO399 is attributed to the shorter leucine side chain in RORα and β which would not reach the phenylalanine on the AF2 helix further underscoring the role of Met358 as a trigger for RORγ specific inverse agonism (Fig. 7a). Furthermore, RORα contains two phenylalanine residues in its LBS whereas RORβ and γ have a leucine in the same position (Fig. 6b). We hypothesize that the two phenylalanine residues in the LBS of RORα occlude the dihydrobenzoxazepinone ring system of BIO399 from binding it and responsible for the increase in selectivity for RORα over β. Conclusions We have identified a novel series of synthetic benzoxazinone ligands which modulate the transcriptional activity of RORγ in a FRET based assay. Using partial proteolysis we show a conformational change which destabilizes the AF2 helix of RORγ when the inverse agonist BIO399 binds. The two RORγ co-crystal structures reported here show how a small change to the core ring system can modulate the mode of action from agonist (BIO592) to inverse agonism (BIO399). Finally, we are reporting a newly identified trigger for achieving RORγ specific inverse agonism in an in vivo setting through Met358 which perturbs the agonist conformation of the AF2 helix and prevents coactivator protein binding. Abbreviations AF2, activation function 2; BisTRIS, 2-[Bis(2-hydroxyethyl)amino]-a-(hydroxymethyl)propane-1,3-diol; DND, DNA binding domain; DTT, 1,4-Dithiothreitol; EDTA, 2-({2-[Bis(carboxymethyl)amino]ethyl}(carboxymethyl)amino)acetic acid; FRET, fluorescence resonance energy transfer; GST, Glutathione-S-Transferase; HEPES, 2-[4(2-hydroxyethyl)-1-piperazineethanesulfonic acid; IC50, half maximal inhibitory concentration; IL-17, Interleukin-17; IPTG, isopropyl β-D-1-thiogalactopyranoside; LBD, Ligand Binding Domain; LBS, ligand binding site; LC-MS, liquid chromatography/mass spectrometry; PDB, Protein Data Bank; ROR, retinoid orphan receptor; SRC-1, steroid receptor coactivator-1; TH17 Cells, T helper cells; TRIS, 2-amino-2-hydroxymethyl-propane-1,3,diol. Additional files Competing interests The authors declare that they have no competing interests. Consent to publish Not applicable. Ethics Not applicable. References Jetten AM. Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism. Nuclear Receptor Signaingl. 2007;4:e003. The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis Increased expression of interleukin 17 in inflammatory bowel disease RORgammat recruits steroid receptor coactivators to ensure thymocyte survival Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha Discovery of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as potent RORγt inverse agonists Wang Y, Cai W, Cheng Y, Yang T, Liu Q, Zhang G, Meng Q, Han F, Huang Y, Zhou L2 Xiang Z, Zhao YG, Xu Y, Cheng Z, Lu S, Wu Q, Xiang JN, Elliott JD, Leung S, Ren F, Lin X. Discovery of Biaryl Amides as Potent, Orally Bioavailable, and CNS Penetrant RORγt Inhibitors. ACS Med Chem Lett. 2015;26:787–92. Fauber BP, René O, Deng Y, DeVoss J, Eidenschenk C, Everett C, Ganguli A1, Gobbi A, Hawkins J1, Johnson AR, La H, Lesch J, Lockey P1, Norman M1, Ouyang W, Summerhill S1, Wong H. Discovery of 1-{4-[3-fluoro-4-((3s,6r)-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone (GNE-3500): a potent, selective, and orally bioavailable retinoic acid receptor-related orphan receptor C (RORc or RORγ) inverse agonist. J Med Chem. 2015;58:5308–22. Discovery of 2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide derivatives as new RORγ inhibitors using virtual screening, synthesis and biological evaluation Chao J, Enyedy IJ, Hutchings RH, Jones HJ, Powell NA, Vanvloten KD. Biaryl-containing compounds as inverse agonists of ror-gamma receptors. PCT Int Appl. 2014, WO2014008214 A1. Selective LXXLL peptides antagonize transcriptional activation by the retinoid-related orphan receptor RORγ iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM Otwinowski Z, Minor W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 1997;276:307–26 Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma Molecular replacement with MOLREP Efficient anisotropic refinement of macromolecular structures using FFT Coot: Model-building tools for molecular graphics ROR nuclear receptors: structures, related diseases, and drug discovery The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen Nuclear receptor ligand-binding domains: reduction of helix H12 dynamics to favor crystallization Ligand-specific structural changes in the vitamin D receptor in solution Use of limited proteolysis to identify protein domains suitable for structural analysis Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc Structural basis of digoxin that antagonizes RORγt receptor activity and suppresses Th17 cell differentiation and interleukin (IL)-17 production Discovery of 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide analogs as new RORC modulators Minor Structural Change to Tertiary Sulfonamide RORc Ligands Led to Opposite Mechanisms of Action Discovery of novel pyrazole-containing benzamides as potent RORγ inverse agonists Discovery of biaryl carboxylamides as potent RORγ inverse agonists","denotations":[{"span":{"begin":36,"end":44},"obj":"0.9996841,protein,cleaner0,2023-07-19T15:12:51Z,PR:","id":"1"},{"span":{"begin":95,"end":108},"obj":"0.9997347,chemical,cleaner0,2023-07-19T15:13:56Z,CHEBI:","id":"2"},{"span":{"begin":131,"end":155},"obj":"0.9994586,protein_type,cleaner0,2023-07-19T15:12:34Z,MESH:","id":"3"},{"span":{"begin":156,"end":160},"obj":"0.9995332,protein,cleaner0,2023-07-19T15:12:44Z,PR:","id":"4"},{"span":{"begin":244,"end":255},"obj":"protein_type,MESH:,cleaner0,2023-07-19T15:55:50Z","id":"836"},{"span":{"begin":256,"end":261},"obj":"protein_type,MESH:,cleaner0,2023-07-19T15:55:24Z","id":"833"},{"span":{"begin":421,"end":425},"obj":"0.99969506,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"6"},{"span":{"begin":491,"end":524},"obj":"structure_element,SO:,cleaner0,2023-07-19T15:13:36Z","id":"781"},{"span":{"begin":532,"end":553},"obj":"0.9996891,structure_element,cleaner0,2023-07-19T15:13:07Z,SO:","id":"9"},{"span":{"begin":557,"end":561},"obj":"0.9997353,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"10"},{"span":{"begin":568,"end":577},"obj":"0.9995486,protein_state,cleaner0,2023-07-19T15:59:12Z,DUMMY:","id":"11"},{"span":{"begin":578,"end":595},"obj":"0.99966925,structure_element,cleaner0,2023-07-19T15:54:48Z,SO:","id":"12"},{"span":{"begin":647,"end":651},"obj":"0.99968076,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"13"},{"span":{"begin":661,"end":676},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"850"},{"span":{"begin":905,"end":918},"obj":"0.99951196,chemical,cleaner0,2023-07-19T15:13:55Z,CHEBI:","id":"14"},{"span":{"begin":937,"end":944},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"879"},{"span":{"begin":946,"end":952},"obj":"0.9995297,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"15"},{"span":{"begin":958,"end":973},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"851"},{"span":{"begin":975,"end":981},"obj":"0.9994516,chemical,cleaner0,2023-07-19T15:14:08Z,CHEBI:","id":"16"},{"span":{"begin":1003,"end":1019},"obj":"0.9995902,experimental_method,cleaner0,2023-07-19T15:14:47Z,MESH:","id":"17"},{"span":{"begin":1038,"end":1047},"obj":"0.9997276,structure_element,cleaner0,2023-07-19T15:14:25Z,SO:","id":"18"},{"span":{"begin":1051,"end":1055},"obj":"0.99978596,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"19"},{"span":{"begin":1059,"end":1084},"obj":"0.7023409,protein_state,cleaner0,2023-07-19T15:59:28Z,DUMMY:","id":"20"},{"span":{"begin":1090,"end":1105},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"852"},{"span":{"begin":1106,"end":1112},"obj":"0.9991371,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"21"},{"span":{"begin":1126,"end":1147},"obj":"0.9995466,experimental_method,cleaner0,2023-07-19T15:14:51Z,MESH:","id":"22"},{"span":{"begin":1187,"end":1200},"obj":"0.9994616,chemical,cleaner0,2023-07-19T15:13:56Z,CHEBI:","id":"23"},{"span":{"begin":1201,"end":1208},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"882"},{"span":{"begin":1209,"end":1215},"obj":"0.9995976,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"24"},{"span":{"begin":1243,"end":1247},"obj":"0.99979097,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"25"},{"span":{"begin":1258,"end":1280},"obj":"0.9995693,experimental_method,cleaner0,2023-07-19T15:14:56Z,MESH:","id":"26"},{"span":{"begin":1299,"end":1314},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"853"},{"span":{"begin":1315,"end":1321},"obj":"0.99939096,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"27"},{"span":{"begin":1348,"end":1352},"obj":"0.9997814,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"28"},{"span":{"begin":1358,"end":1361},"obj":"0.99713814,protein_type,cleaner0,2023-07-19T15:14:21Z,MESH:","id":"29"},{"span":{"begin":1381,"end":1382},"obj":"0.99299026,protein,cleaner0,2023-07-19T15:16:12Z,PR:","id":"30"},{"span":{"begin":1387,"end":1388},"obj":"0.9972766,protein,cleaner0,2023-07-19T15:16:15Z,PR:","id":"31"},{"span":{"begin":1434,"end":1447},"obj":"0.9997489,chemical,cleaner0,2023-07-19T15:13:56Z,CHEBI:","id":"32"},{"span":{"begin":1474,"end":1484},"obj":"0.99962234,experimental_method,cleaner0,2023-07-19T15:15:18Z,MESH:","id":"33"},{"span":{"begin":1493,"end":1500},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"884"},{"span":{"begin":1502,"end":1508},"obj":"0.999524,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"34"},{"span":{"begin":1513,"end":1528},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"854"},{"span":{"begin":1530,"end":1536},"obj":"0.9993519,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"35"},{"span":{"begin":1581,"end":1588},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"886"},{"span":{"begin":1605,"end":1609},"obj":"0.9997969,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"36"},{"span":{"begin":1646,"end":1655},"obj":"0.9997283,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"37"},{"span":{"begin":1659,"end":1663},"obj":"0.99979514,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"38"},{"span":{"begin":1703,"end":1709},"obj":"0.9988256,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"39"},{"span":{"begin":1710,"end":1725},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"855"},{"span":{"begin":1749,"end":1781},"obj":"0.99966204,site,cleaner0,2023-07-19T15:15:29Z,SO:","id":"40"},{"span":{"begin":1787,"end":1811},"obj":"0.9996029,experimental_method,cleaner0,2023-07-19T15:15:07Z,MESH:","id":"41"},{"span":{"begin":1819,"end":1825},"obj":"0.99946314,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"42"},{"span":{"begin":1826,"end":1833},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"888"},{"span":{"begin":1838,"end":1844},"obj":"0.9992617,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"43"},{"span":{"begin":1845,"end":1860},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"856"},{"span":{"begin":1861,"end":1871},"obj":"0.9992576,evidence,cleaner0,2023-07-19T15:50:19Z,DUMMY:","id":"44"},{"span":{"begin":1891,"end":1897},"obj":"0.9998889,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"45"},{"span":{"begin":1901,"end":1905},"obj":"0.9997987,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"46"},{"span":{"begin":1925,"end":1929},"obj":"0.99973875,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"47"},{"span":{"begin":2157,"end":2195},"obj":"protein,PR:,cleaner0,2023-07-19T15:15:55Z","id":"801"},{"span":{"begin":2197,"end":2201},"obj":"0.99976176,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"51"},{"span":{"begin":2208,"end":2228},"obj":"0.96197236,protein_type,cleaner0,2023-07-19T15:16:22Z,MESH:","id":"52"},{"span":{"begin":2258,"end":2275},"obj":"0.9992901,protein_type,cleaner0,2023-07-19T15:16:28Z,MESH:","id":"53"},{"span":{"begin":2318,"end":2322},"obj":"0.9998398,protein,cleaner0,2023-07-19T15:16:01Z,PR:","id":"54"},{"span":{"begin":2327,"end":2331},"obj":"0.99984014,protein,cleaner0,2023-07-19T15:16:06Z,PR:","id":"55"},{"span":{"begin":2401,"end":2405},"obj":"0.99961334,protein_type,cleaner0,2023-07-19T15:16:33Z,MESH:","id":"56"},{"span":{"begin":2543,"end":2547},"obj":"0.99953103,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"57"},{"span":{"begin":2722,"end":2727},"obj":"0.9956913,protein_type,cleaner0,2023-07-19T15:55:24Z,MESH:","id":"59"},{"span":{"begin":2740,"end":2745},"obj":"0.99601126,protein_type,cleaner0,2023-07-19T15:55:24Z,MESH:","id":"60"},{"span":{"begin":2768,"end":2779},"obj":"protein_type,MESH:,cleaner0,2023-07-19T15:55:50Z","id":"837"},{"span":{"begin":2937,"end":2941},"obj":"0.9997352,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"61"},{"span":{"begin":2995,"end":2999},"obj":"0.9995522,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"62"},{"span":{"begin":3026,"end":3044},"obj":"0.99970484,structure_element,cleaner0,2023-07-19T15:16:52Z,SO:","id":"63"},{"span":{"begin":3046,"end":3049},"obj":"0.9998134,structure_element,cleaner0,2023-07-19T15:16:57Z,SO:","id":"64"},{"span":{"begin":3077,"end":3098},"obj":"0.999716,structure_element,cleaner0,2023-07-19T15:13:08Z,SO:","id":"65"},{"span":{"begin":3100,"end":3103},"obj":"0.9998136,structure_element,cleaner0,2023-07-19T15:17:06Z,SO:","id":"66"},{"span":{"begin":3120,"end":3132},"obj":"0.9997424,structure_element,cleaner0,2023-07-19T15:17:15Z,SO:","id":"68"},{"span":{"begin":3138,"end":3141},"obj":"0.9998217,structure_element,cleaner0,2023-07-19T15:16:57Z,SO:","id":"69"},{"span":{"begin":3161,"end":3173},"obj":"0.99940574,structure_element,cleaner0,2023-07-19T15:17:20Z,SO:","id":"70"},{"span":{"begin":3256,"end":3290},"obj":"structure_element,SO:,cleaner0,2023-07-19T15:17:55Z","id":"802"},{"span":{"begin":3296,"end":3299},"obj":"0.99982005,structure_element,cleaner0,2023-07-19T15:17:06Z,SO:","id":"73"},{"span":{"begin":3314,"end":3348},"obj":"0.9995779,site,cleaner0,2023-07-19T15:17:29Z,SO:","id":"74"},{"span":{"begin":3355,"end":3386},"obj":"0.99728817,site,cleaner0,2023-07-19T15:18:04Z,SO:","id":"75"},{"span":{"begin":3388,"end":3391},"obj":"0.97560805,site,cleaner0,2023-07-19T15:18:14Z,SO:","id":"76"},{"span":{"begin":3449,"end":3475},"obj":"0.9996037,site,cleaner0,2023-07-19T15:18:21Z,SO:","id":"77"},{"span":{"begin":3479,"end":3483},"obj":"0.99960774,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"78"},{"span":{"begin":3497,"end":3506},"obj":"0.9993538,protein_state,cleaner0,2023-07-19T16:00:23Z,DUMMY:","id":"79"},{"span":{"begin":3507,"end":3524},"obj":"structure_element,SO:,cleaner0,2023-07-19T15:58:57Z","id":"849"},{"span":{"begin":3652,"end":3677},"obj":"0.99955034,protein_type,cleaner0,2023-07-19T15:18:38Z,MESH:","id":"82"},{"span":{"begin":3679,"end":3683},"obj":"0.99942905,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"83"},{"span":{"begin":3686,"end":3693},"obj":"0.9998221,structure_element,cleaner0,2023-07-19T15:18:45Z,SO:","id":"84"},{"span":{"begin":3730,"end":3733},"obj":"0.99983406,structure_element,cleaner0,2023-07-19T15:17:06Z,SO:","id":"85"},{"span":{"begin":3762,"end":3788},"obj":"0.9996125,site,cleaner0,2023-07-19T15:18:21Z,SO:","id":"86"},{"span":{"begin":3824,"end":3851},"obj":"0.9996948,structure_element,cleaner0,2023-07-19T15:18:49Z,SO:","id":"87"},{"span":{"begin":3853,"end":3856},"obj":"0.99982625,structure_element,cleaner0,2023-07-19T15:18:51Z,SO:","id":"88"},{"span":{"begin":3862,"end":3866},"obj":"0.9995863,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"89"},{"span":{"begin":3892,"end":3901},"obj":"0.99973696,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"90"},{"span":{"begin":3923,"end":3949},"obj":"0.99961215,site,cleaner0,2023-07-19T15:18:21Z,SO:","id":"91"},{"span":{"begin":3967,"end":3978},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"947"},{"span":{"begin":3987,"end":3993},"obj":"0.9999027,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"92"},{"span":{"begin":3998,"end":4004},"obj":"0.99989915,residue_name_number,cleaner0,2023-07-19T15:18:56Z,DUMMY:","id":"93"},{"span":{"begin":4020,"end":4037},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"948"},{"span":{"begin":4046,"end":4052},"obj":"0.99990165,residue_name_number,cleaner0,2023-07-19T15:18:56Z,DUMMY:","id":"94"},{"span":{"begin":4057,"end":4063},"obj":"0.99990034,residue_name_number,cleaner0,2023-07-19T15:19:01Z,DUMMY:","id":"95"},{"span":{"begin":4089,"end":4098},"obj":"0.9997456,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"96"},{"span":{"begin":4156,"end":4159},"obj":"0.99979895,site,cleaner0,2023-07-19T15:18:14Z,SO:","id":"97"},{"span":{"begin":4314,"end":4318},"obj":"0.9995858,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"98"},{"span":{"begin":4484,"end":4488},"obj":"0.9994648,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"99"},{"span":{"begin":4599,"end":4611},"obj":"evidence,DUMMY:,cleaner0,2023-07-19T15:20:05Z","id":"804"},{"span":{"begin":4616,"end":4623},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"890"},{"span":{"begin":4624,"end":4630},"obj":"0.9992667,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"101"},{"span":{"begin":4639,"end":4654},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"857"},{"span":{"begin":4655,"end":4661},"obj":"0.99943894,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"102"},{"span":{"begin":4718,"end":4731},"obj":"0.9993067,chemical,cleaner0,2023-07-19T15:13:56Z,CHEBI:","id":"103"},{"span":{"begin":4732,"end":4736},"obj":"0.99667335,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"104"},{"span":{"begin":4753,"end":4760},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"892"},{"span":{"begin":4761,"end":4767},"obj":"0.9994783,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"105"},{"span":{"begin":4785,"end":4800},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"858"},{"span":{"begin":4801,"end":4807},"obj":"0.99941254,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"106"},{"span":{"begin":4848,"end":4905},"obj":"experimental_method,MESH:,cleaner0,2023-07-19T15:19:33Z","id":"803"},{"span":{"begin":4960,"end":4979},"obj":"0.99953055,experimental_method,cleaner0,2023-07-19T15:19:44Z,MESH:","id":"109"},{"span":{"begin":5000,"end":5017},"obj":"0.99952245,experimental_method,cleaner0,2023-07-19T15:19:46Z,MESH:","id":"110"},{"span":{"begin":5051,"end":5060},"obj":"0.9997479,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"111"},{"span":{"begin":5064,"end":5068},"obj":"0.999608,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"112"},{"span":{"begin":5087,"end":5093},"obj":"0.9987185,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"113"},{"span":{"begin":5095,"end":5110},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"859"},{"span":{"begin":5140,"end":5153},"obj":"0.9855926,evidence,cleaner0,2023-07-19T15:50:30Z,DUMMY:","id":"114"},{"span":{"begin":5161,"end":5174},"obj":"0.99849415,chemical,cleaner0,2023-07-19T15:13:56Z,CHEBI:","id":"115"},{"span":{"begin":5175,"end":5179},"obj":"0.99864763,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"116"},{"span":{"begin":5180,"end":5198},"obj":"0.99943864,evidence,cleaner0,2023-07-19T15:50:34Z,DUMMY:","id":"117"},{"span":{"begin":5208,"end":5211},"obj":"0.99912757,protein_type,cleaner0,2023-07-19T15:14:21Z,MESH:","id":"118"},{"span":{"begin":5212,"end":5222},"obj":"0.9982961,evidence,cleaner0,2023-07-19T15:20:17Z,DUMMY:","id":"119"},{"span":{"begin":10979,"end":10995},"obj":"0.99959534,experimental_method,cleaner0,2023-07-19T15:14:47Z,MESH:","id":"251"},{"span":{"begin":11010,"end":11017},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"898"},{"span":{"begin":11018,"end":11024},"obj":"0.9988141,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"252"},{"span":{"begin":11075,"end":11082},"obj":"0.48274022,chemical,cleaner0,2023-07-19T16:06:11Z,CHEBI:","id":"253"},{"span":{"begin":11098,"end":11102},"obj":"0.99982065,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"254"},{"span":{"begin":11104,"end":11108},"obj":"0.99535024,evidence,cleaner0,2023-07-19T15:20:56Z,DUMMY:","id":"255"},{"span":{"begin":11121,"end":11125},"obj":"0.9963708,evidence,cleaner0,2023-07-19T15:21:01Z,DUMMY:","id":"256"},{"span":{"begin":11149,"end":11164},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"861"},{"span":{"begin":11165,"end":11171},"obj":"0.9961767,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"257"},{"span":{"begin":11223,"end":11227},"obj":"0.9992803,evidence,cleaner0,2023-07-19T15:50:45Z,DUMMY:","id":"258"},{"span":{"begin":11290,"end":11297},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"900"},{"span":{"begin":11298,"end":11304},"obj":"0.9986708,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"259"},{"span":{"begin":11309,"end":11324},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"862"},{"span":{"begin":11325,"end":11331},"obj":"0.9949522,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"260"},{"span":{"begin":11352,"end":11387},"obj":"0.9993613,chemical,cleaner0,2023-07-19T15:21:29Z,CHEBI:","id":"261"},{"span":{"begin":11403,"end":11409},"obj":"0.9886368,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"262"},{"span":{"begin":11440,"end":11463},"obj":"0.99949,chemical,cleaner0,2023-07-19T15:21:40Z,CHEBI:","id":"263"},{"span":{"begin":11479,"end":11485},"obj":"0.9971795,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"264"},{"span":{"begin":11639,"end":11645},"obj":"0.9968554,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"265"},{"span":{"begin":11650,"end":11656},"obj":"0.9926582,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"266"},{"span":{"begin":11664,"end":11667},"obj":"0.9996377,site,cleaner0,2023-07-19T15:18:14Z,SO:","id":"267"},{"span":{"begin":11671,"end":11675},"obj":"0.99981266,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"268"},{"span":{"begin":11682,"end":11703},"obj":"0.99956167,experimental_method,cleaner0,2023-07-19T15:14:52Z,MESH:","id":"269"},{"span":{"begin":11713,"end":11722},"obj":"0.71792406,evidence,cleaner0,2023-07-19T15:50:51Z,DUMMY:","id":"270"},{"span":{"begin":11730,"end":11750},"obj":"0.9997385,complex_assembly,cleaner0,2023-07-19T15:21:15Z,GO:","id":"271"},{"span":{"begin":11793,"end":11799},"obj":"0.6499308,protein_state,cleaner0,2023-07-19T15:21:52Z,DUMMY:","id":"272"},{"span":{"begin":11824,"end":11841},"obj":"0.88747376,evidence,cleaner0,2023-07-19T15:50:58Z,DUMMY:","id":"273"},{"span":{"begin":11845,"end":11852},"obj":"0.99852496,protein,cleaner0,2023-07-19T15:23:34Z,PR:","id":"274"},{"span":{"begin":11853,"end":11859},"obj":"0.97716755,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"275"},{"span":{"begin":11864,"end":11869},"obj":"0.99978215,chemical,cleaner0,2023-07-19T15:23:28Z,CHEBI:","id":"276"},{"span":{"begin":11873,"end":11877},"obj":"0.9997538,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"277"},{"span":{"begin":11878,"end":11887},"obj":"0.99961114,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"278"},{"span":{"begin":11895,"end":11902},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"902"},{"span":{"begin":11919,"end":11924},"obj":"0.9998048,chemical,cleaner0,2023-07-19T15:23:28Z,CHEBI:","id":"279"},{"span":{"begin":11945,"end":11953},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T15:24:07Z","id":"818"},{"span":{"begin":11958,"end":11976},"obj":"0.9995923,site,cleaner0,2023-07-19T15:23:47Z,SO:","id":"281"},{"span":{"begin":11980,"end":11984},"obj":"0.9994972,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"282"},{"span":{"begin":11997,"end":12004},"obj":"0.9997739,protein,cleaner0,2023-07-19T15:23:34Z,PR:","id":"283"},{"span":{"begin":12005,"end":12013},"obj":"0.9995284,protein_state,cleaner0,2023-07-19T15:24:12Z,DUMMY:","id":"284"},{"span":{"begin":12014,"end":12021},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"903"},{"span":{"begin":12022,"end":12028},"obj":"0.99953663,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"285"},{"span":{"begin":12033,"end":12045},"obj":"0.9996308,experimental_method,cleaner0,2023-07-19T15:52:21Z,MESH:","id":"286"},{"span":{"begin":12053,"end":12062},"obj":"0.9987739,protein_state,cleaner0,2023-07-19T16:00:29Z,DUMMY:","id":"287"},{"span":{"begin":12095,"end":12100},"obj":"0.96395886,chemical,cleaner0,2023-07-19T15:23:27Z,CHEBI:","id":"288"},{"span":{"begin":12141,"end":12150},"obj":"0.9991172,evidence,cleaner0,2023-07-19T15:51:05Z,DUMMY:","id":"289"},{"span":{"begin":12204,"end":12207},"obj":"0.99873656,protein_type,cleaner0,2023-07-19T15:14:21Z,MESH:","id":"291"},{"span":{"begin":12208,"end":12215},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"904"},{"span":{"begin":12228,"end":12238},"obj":"0.9898212,evidence,cleaner0,2023-07-19T15:51:13Z,DUMMY:","id":"292"},{"span":{"begin":12244,"end":12268},"obj":"0.99713844,protein_state,cleaner0,2023-07-19T15:25:01Z,DUMMY:","id":"293"},{"span":{"begin":12269,"end":12301},"obj":"0.99960726,protein_state,cleaner0,2023-07-19T15:25:14Z,DUMMY:","id":"294"},{"span":{"begin":12311,"end":12320},"obj":"0.9997512,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"295"},{"span":{"begin":12328,"end":12335},"obj":"0.9995945,protein_state,cleaner0,2023-07-19T16:00:34Z,DUMMY:","id":"296"},{"span":{"begin":12354,"end":12361},"obj":"0.9995764,protein_state,cleaner0,2023-07-19T16:00:38Z,DUMMY:","id":"297"},{"span":{"begin":12394,"end":12407},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"935"},{"span":{"begin":12416,"end":12422},"obj":"0.99990356,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"298"},{"span":{"begin":12427,"end":12433},"obj":"0.9998977,residue_name_number,cleaner0,2023-07-19T15:18:57Z,DUMMY:","id":"299"},{"span":{"begin":12450,"end":12466},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"939"},{"span":{"begin":12475,"end":12481},"obj":"0.99989974,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"300"},{"span":{"begin":12483,"end":12489},"obj":"0.9998951,residue_name_number,cleaner0,2023-07-19T15:18:57Z,DUMMY:","id":"301"},{"span":{"begin":12494,"end":12500},"obj":"0.9998956,residue_name_number,cleaner0,2023-07-19T15:19:02Z,DUMMY:","id":"302"},{"span":{"begin":12516,"end":12529},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"936"},{"span":{"begin":12538,"end":12544},"obj":"0.99989986,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"303"},{"span":{"begin":12549,"end":12555},"obj":"0.99989367,residue_name_number,cleaner0,2023-07-19T15:18:57Z,DUMMY:","id":"304"},{"span":{"begin":12593,"end":12597},"obj":"0.83831507,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"305"},{"span":{"begin":12598,"end":12605},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"905"},{"span":{"begin":12652,"end":12663},"obj":"0.9996239,experimental_method,cleaner0,2023-07-19T15:25:38Z,MESH:","id":"306"},{"span":{"begin":12700,"end":12704},"obj":"0.99961555,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"307"},{"span":{"begin":12788,"end":12797},"obj":"0.99976134,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"308"},{"span":{"begin":12831,"end":12857},"obj":"0.99962956,site,cleaner0,2023-07-19T15:18:21Z,SO:","id":"309"},{"span":{"begin":12916,"end":12932},"obj":"0.99952424,evidence,cleaner0,2023-07-19T15:25:47Z,DUMMY:","id":"310"},{"span":{"begin":12961,"end":12966},"obj":"0.9981281,chemical,cleaner0,2023-07-19T15:23:28Z,CHEBI:","id":"311"},{"span":{"begin":12993,"end":13003},"obj":"0.7580885,structure_element,cleaner0,2023-07-19T15:25:52Z,SO:","id":"312"},{"span":{"begin":13019,"end":13026},"obj":"0.99970657,structure_element,cleaner0,2023-07-19T15:25:58Z,SO:","id":"313"},{"span":{"begin":13046,"end":13070},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"940"},{"span":{"begin":13080,"end":13106},"obj":"0.999589,site,cleaner0,2023-07-19T15:18:21Z,SO:","id":"314"},{"span":{"begin":13110,"end":13114},"obj":"0.9997904,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"315"},{"span":{"begin":13175,"end":13184},"obj":"0.99953485,protein_state,cleaner0,2023-07-19T15:26:40Z,DUMMY:","id":"316"},{"span":{"begin":13185,"end":13198},"obj":"0.9152874,structure_element,cleaner0,2023-07-19T15:26:31Z,SO:","id":"317"},{"span":{"begin":13229,"end":13233},"obj":"0.9999007,residue_name_number,cleaner0,2023-07-19T15:26:12Z,DUMMY:","id":"318"},{"span":{"begin":13250,"end":13255},"obj":"0.99990094,residue_name_number,cleaner0,2023-07-19T15:26:17Z,DUMMY:","id":"319"},{"span":{"begin":13259,"end":13264},"obj":"0.99767834,chemical,cleaner0,2023-07-19T15:23:28Z,CHEBI:","id":"320"},{"span":{"begin":13270,"end":13284},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"943"},{"span":{"begin":13290,"end":13296},"obj":"0.9999043,residue_name_number,cleaner0,2023-07-19T15:26:23Z,DUMMY:","id":"321"},{"span":{"begin":13298,"end":13305},"obj":"0.9997838,structure_element,cleaner0,2023-07-19T15:18:45Z,SO:","id":"322"},{"span":{"begin":13311,"end":13317},"obj":"0.9999033,residue_name_number,cleaner0,2023-07-19T15:26:27Z,DUMMY:","id":"323"},{"span":{"begin":13319,"end":13325},"obj":"0.9997806,structure_element,cleaner0,2023-07-19T15:26:49Z,SO:","id":"324"},{"span":{"begin":13330,"end":13334},"obj":"0.9997863,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"325"},{"span":{"begin":13354,"end":13367},"obj":"0.85428715,structure_element,cleaner0,2023-07-19T15:26:32Z,SO:","id":"326"},{"span":{"begin":13385,"end":13389},"obj":"0.999788,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"327"},{"span":{"begin":13489,"end":13506},"obj":"0.9995812,experimental_method,cleaner0,2023-07-19T15:26:37Z,MESH:","id":"328"},{"span":{"begin":13539,"end":13545},"obj":"0.9965342,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"329"},{"span":{"begin":13557,"end":13566},"obj":"0.999559,protein_state,cleaner0,2023-07-19T15:27:02Z,DUMMY:","id":"330"},{"span":{"begin":13596,"end":13603},"obj":"0.6351255,protein_state,cleaner0,2023-07-19T15:27:05Z,DUMMY:","id":"331"},{"span":{"begin":13620,"end":13624},"obj":"0.99970454,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"332"},{"span":{"begin":13658,"end":13665},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"906"},{"span":{"begin":13666,"end":13672},"obj":"0.9995141,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"333"},{"span":{"begin":13692,"end":13695},"obj":"0.6673667,site,cleaner0,2023-07-19T15:18:14Z,SO:","id":"334"},{"span":{"begin":13699,"end":13703},"obj":"0.999788,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"335"},{"span":{"begin":13707,"end":13720},"obj":"chemical,CHEBI:,cleaner0,2023-07-19T15:13:56Z","id":"782"},{"span":{"begin":13736,"end":13743},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"907"},{"span":{"begin":13744,"end":13750},"obj":"0.99953103,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"336"},{"span":{"begin":13767,"end":13773},"obj":"0.9998983,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"337"},{"span":{"begin":13777,"end":13781},"obj":"0.9997874,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"338"},{"span":{"begin":13794,"end":13801},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"908"},{"span":{"begin":13822,"end":13831},"obj":"0.99967206,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"339"},{"span":{"begin":13840,"end":13846},"obj":"0.9990957,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"340"},{"span":{"begin":13847,"end":13855},"obj":"0.9857471,protein_state,cleaner0,2023-07-19T15:24:08Z,DUMMY:","id":"341"},{"span":{"begin":13858,"end":13867},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T15:27:48Z","id":"819"},{"span":{"begin":13896,"end":13899},"obj":"0.99963737,site,cleaner0,2023-07-19T15:18:14Z,SO:","id":"343"},{"span":{"begin":13903,"end":13907},"obj":"0.99978584,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"344"},{"span":{"begin":13917,"end":13923},"obj":"0.99809307,chemical,cleaner0,2023-07-19T15:29:29Z,CHEBI:","id":"345"},{"span":{"begin":13961,"end":13967},"obj":"0.99882764,site,cleaner0,2023-07-19T15:54:20Z,SO:","id":"346"},{"span":{"begin":13975,"end":13999},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"941"},{"span":{"begin":14005,"end":14011},"obj":"0.9999033,residue_name_number,cleaner0,2023-07-19T15:28:06Z,DUMMY:","id":"347"},{"span":{"begin":14013,"end":14019},"obj":"0.9998995,residue_name_number,cleaner0,2023-07-19T15:28:10Z,DUMMY:","id":"348"},{"span":{"begin":14021,"end":14027},"obj":"0.99989617,residue_name_number,cleaner0,2023-07-19T15:28:14Z,DUMMY:","id":"349"},{"span":{"begin":14032,"end":14038},"obj":"0.9998977,residue_name_number,cleaner0,2023-07-19T15:28:19Z,DUMMY:","id":"350"},{"span":{"begin":14049,"end":14068},"obj":"0.9988957,chemical,cleaner0,2023-07-19T15:29:27Z,CHEBI:","id":"351"},{"span":{"begin":14089,"end":14113},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"942"},{"span":{"begin":14119,"end":14125},"obj":"0.9999012,residue_name_number,cleaner0,2023-07-19T15:28:25Z,DUMMY:","id":"352"},{"span":{"begin":14127,"end":14133},"obj":"0.999899,residue_name_number,cleaner0,2023-07-19T15:28:29Z,DUMMY:","id":"353"},{"span":{"begin":14135,"end":14141},"obj":"0.9999006,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"354"},{"span":{"begin":14143,"end":14149},"obj":"0.9999014,residue_name_number,cleaner0,2023-07-19T15:28:37Z,DUMMY:","id":"355"},{"span":{"begin":14151,"end":14158},"obj":"residue_name_number,DUMMY:,cleaner0,2023-07-19T15:28:56Z","id":"820"},{"span":{"begin":14163,"end":14169},"obj":"0.9999039,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"358"},{"span":{"begin":14204,"end":14212},"obj":"0.97242635,chemical,cleaner0,2023-07-19T15:29:34Z,CHEBI:","id":"359"},{"span":{"begin":14245,"end":14251},"obj":"0.9925991,site,cleaner0,2023-07-19T15:54:25Z,SO:","id":"360"},{"span":{"begin":14275,"end":14294},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"944"},{"span":{"begin":14300,"end":14306},"obj":"0.99990606,residue_name_number,cleaner0,2023-07-19T15:29:06Z,DUMMY:","id":"362"},{"span":{"begin":14308,"end":14331},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"945"},{"span":{"begin":14363,"end":14376},"obj":"0.9993363,chemical,cleaner0,2023-07-19T15:13:56Z,CHEBI:","id":"363"},{"span":{"begin":14381,"end":14387},"obj":"0.9999043,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"364"},{"span":{"begin":14402,"end":14408},"obj":"0.999907,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"365"},{"span":{"begin":14443,"end":14456},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"937"},{"span":{"begin":14462,"end":14468},"obj":"0.99990344,residue_name_number,cleaner0,2023-07-19T15:18:57Z,DUMMY:","id":"366"},{"span":{"begin":14493,"end":14500},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"909"},{"span":{"begin":14529,"end":14533},"obj":"0.999711,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"367"},{"span":{"begin":14534,"end":14543},"obj":"0.99974036,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"368"},{"span":{"begin":14579,"end":14590},"obj":"0.9675162,protein_state,cleaner0,2023-07-19T15:29:49Z,DUMMY:","id":"369"},{"span":{"begin":14591,"end":14606},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"863"},{"span":{"begin":14607,"end":14613},"obj":"0.9995938,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"370"},{"span":{"begin":14637,"end":14655},"obj":"0.999572,experimental_method,cleaner0,2023-07-19T15:30:01Z,MESH:","id":"371"},{"span":{"begin":14665,"end":14680},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"864"},{"span":{"begin":14681,"end":14687},"obj":"0.9988544,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"372"},{"span":{"begin":14708,"end":14723},"obj":"0.99946946,experimental_method,cleaner0,2023-07-19T15:29:54Z,MESH:","id":"373"},{"span":{"begin":14737,"end":14743},"obj":"0.9979844,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"374"},{"span":{"begin":14748,"end":14755},"obj":"0.9996563,protein,cleaner0,2023-07-19T15:23:34Z,PR:","id":"375"},{"span":{"begin":14765,"end":14768},"obj":"0.9412052,structure_element,cleaner0,2023-07-19T15:59:05Z,SO:","id":"376"},{"span":{"begin":14769,"end":14775},"obj":"0.9938573,protein_state,cleaner0,2023-07-19T15:30:12Z,DUMMY:","id":"377"},{"span":{"begin":14803,"end":14811},"obj":"0.9034121,evidence,cleaner0,2023-07-19T15:30:17Z,DUMMY:","id":"378"},{"span":{"begin":14838,"end":14845},"obj":"0.9997154,protein,cleaner0,2023-07-19T15:23:34Z,PR:","id":"379"},{"span":{"begin":14885,"end":14895},"obj":"0.9995203,experimental_method,cleaner0,2023-07-19T15:15:19Z,MESH:","id":"380"},{"span":{"begin":14915,"end":14921},"obj":"0.99598217,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"381"},{"span":{"begin":14977,"end":14986},"obj":"0.9997167,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"382"},{"span":{"begin":15018,"end":15033},"obj":"0.9927527,experimental_method,cleaner0,2023-07-19T15:30:05Z,MESH:","id":"383"},{"span":{"begin":15077,"end":15084},"obj":"0.99923706,protein,cleaner0,2023-07-19T15:23:34Z,PR:","id":"384"},{"span":{"begin":15090,"end":15102},"obj":"0.9101149,experimental_method,cleaner0,2023-07-19T15:52:27Z,MESH:","id":"385"},{"span":{"begin":15103,"end":15113},"obj":"0.9971443,protein,cleaner0,2023-07-19T15:53:23Z,PR:","id":"386"},{"span":{"begin":15138,"end":15149},"obj":"0.99917436,protein_state,cleaner0,2023-07-19T15:29:49Z,DUMMY:","id":"388"},{"span":{"begin":15150,"end":15156},"obj":"0.999374,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"389"},{"span":{"begin":15174,"end":15191},"obj":"0.99941564,site,cleaner0,2023-07-19T15:54:37Z,SO:","id":"390"},{"span":{"begin":15226,"end":15235},"obj":"0.9997374,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"391"},{"span":{"begin":15264,"end":15289},"obj":"0.9996216,protein_type,cleaner0,2023-07-19T15:18:39Z,MESH:","id":"392"},{"span":{"begin":15295,"end":15303},"obj":"0.99951684,protein_state,cleaner0,2023-07-19T15:24:12Z,DUMMY:","id":"393"},{"span":{"begin":15307,"end":15322},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"865"},{"span":{"begin":15346,"end":15365},"obj":"0.99952674,experimental_method,cleaner0,2023-07-19T15:31:34Z,MESH:","id":"394"},{"span":{"begin":15386,"end":15403},"obj":"0.9995297,experimental_method,cleaner0,2023-07-19T15:31:30Z,MESH:","id":"395"},{"span":{"begin":15420,"end":15426},"obj":"0.99214536,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"396"},{"span":{"begin":15443,"end":15452},"obj":"0.9997202,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"397"},{"span":{"begin":15479,"end":15501},"obj":"0.7968726,experimental_method,cleaner0,2023-07-19T15:31:25Z,MESH:","id":"398"},{"span":{"begin":15517,"end":15524},"obj":"0.9997969,protein,cleaner0,2023-07-19T15:23:34Z,PR:","id":"399"},{"span":{"begin":15549,"end":15556},"obj":"0.99978536,protein,cleaner0,2023-07-19T15:23:34Z,PR:","id":"401"},{"span":{"begin":15562,"end":15569},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"913"},{"span":{"begin":15570,"end":15576},"obj":"0.9989819,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"402"},{"span":{"begin":15593,"end":15598},"obj":"0.9997379,chemical,cleaner0,2023-07-19T15:23:28Z,CHEBI:","id":"403"},{"span":{"begin":15610,"end":15621},"obj":"0.99913347,protein_state,cleaner0,2023-07-19T15:29:49Z,DUMMY:","id":"404"},{"span":{"begin":15622,"end":15637},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"866"},{"span":{"begin":15638,"end":15644},"obj":"0.99921584,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"405"},{"span":{"begin":15687,"end":15708},"obj":"0.99508756,evidence,cleaner0,2023-07-19T15:31:16Z,DUMMY:","id":"406"},{"span":{"begin":15751,"end":15760},"obj":"0.9997283,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"407"},{"span":{"begin":15764,"end":15774},"obj":"0.9967369,protein,cleaner0,2023-07-19T15:53:23Z,PR:","id":"408"},{"span":{"begin":15778,"end":15785},"obj":"0.99980134,protein,cleaner0,2023-07-19T15:23:34Z,PR:","id":"409"},{"span":{"begin":15803,"end":15813},"obj":"residue_range,DUMMY:,cleaner0,2023-07-19T15:48:58Z","id":"825"},{"span":{"begin":15823,"end":15838},"obj":"0.80447483,protein_state,cleaner0,2023-07-19T16:00:48Z,DUMMY:","id":"413"},{"span":{"begin":15876,"end":15879},"obj":"0.43031177,residue_number,cleaner0,2023-07-19T15:49:44Z,DUMMY:","id":"414"},{"span":{"begin":15880,"end":15883},"obj":"residue_number,DUMMY:,cleaner0,2023-07-19T15:49:25Z","id":"826"},{"span":{"begin":15922,"end":15933},"obj":"0.999481,protein_state,cleaner0,2023-07-19T15:29:49Z,DUMMY:","id":"415"},{"span":{"begin":15934,"end":15949},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"867"},{"span":{"begin":15950,"end":15956},"obj":"0.99928194,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"416"},{"span":{"begin":15962,"end":15981},"obj":"0.9842393,evidence,cleaner0,2023-07-19T15:31:19Z,DUMMY:","id":"417"},{"span":{"begin":16084,"end":16087},"obj":"0.49895975,residue_number,cleaner0,2023-07-19T15:49:48Z,DUMMY:","id":"418"},{"span":{"begin":16088,"end":16091},"obj":"residue_number,DUMMY:,cleaner0,2023-07-19T15:49:40Z","id":"827"},{"span":{"begin":16132,"end":16141},"obj":"0.9997306,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"419"},{"span":{"begin":16165,"end":16168},"obj":"0.99967384,protein_state,cleaner0,2023-07-19T16:00:53Z,DUMMY:","id":"420"},{"span":{"begin":16172,"end":16195},"obj":"0.7635996,protein_state,cleaner0,2023-07-19T16:01:01Z,DUMMY:","id":"421"},{"span":{"begin":16255,"end":16272},"obj":"0.999603,experimental_method,cleaner0,2023-07-19T15:32:05Z,MESH:","id":"422"},{"span":{"begin":16287,"end":16294},"obj":"0.9997676,protein,cleaner0,2023-07-19T15:23:34Z,PR:","id":"423"},{"span":{"begin":16304,"end":16308},"obj":"0.9812258,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"424"},{"span":{"begin":16309,"end":16318},"obj":"0.99960935,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"425"},{"span":{"begin":16341,"end":16355},"obj":"0.99924374,protein_state,cleaner0,2023-07-19T15:31:42Z,DUMMY:","id":"426"},{"span":{"begin":16356,"end":16362},"obj":"0.88344735,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"427"},{"span":{"begin":16380,"end":16388},"obj":"0.97513825,evidence,cleaner0,2023-07-19T15:32:18Z,DUMMY:","id":"428"},{"span":{"begin":16426,"end":16434},"obj":"0.8911621,evidence,cleaner0,2023-07-19T15:32:16Z,DUMMY:","id":"429"},{"span":{"begin":16459,"end":16468},"obj":"0.9997282,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"430"},{"span":{"begin":16480,"end":16486},"obj":"0.96908194,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"431"},{"span":{"begin":16528,"end":16536},"obj":"0.99956316,protein_state,cleaner0,2023-07-19T15:32:14Z,DUMMY:","id":"432"},{"span":{"begin":16537,"end":16546},"obj":"0.99973404,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"433"},{"span":{"begin":16553,"end":16564},"obj":"0.99730253,experimental_method,cleaner0,2023-07-19T15:32:09Z,MESH:","id":"434"},{"span":{"begin":16616,"end":16631},"obj":"0.99929774,experimental_method,cleaner0,2023-07-19T15:32:11Z,MESH:","id":"435"},{"span":{"begin":16641,"end":16654},"obj":"0.99842143,protein_state,cleaner0,2023-07-19T15:32:36Z,DUMMY:","id":"436"},{"span":{"begin":16655,"end":16666},"obj":"0.99530745,complex_assembly,cleaner0,2023-07-19T15:32:42Z,GO:","id":"437"},{"span":{"begin":16695,"end":16710},"obj":"0.9996778,experimental_method,cleaner0,2023-07-19T15:32:39Z,MESH:","id":"438"},{"span":{"begin":16729,"end":16738},"obj":"0.9753916,evidence,cleaner0,2023-07-19T15:32:53Z,DUMMY:","id":"439"},{"span":{"begin":16742,"end":16755},"obj":"0.99942464,protein_state,cleaner0,2023-07-19T16:01:07Z,DUMMY:","id":"440"},{"span":{"begin":16756,"end":16760},"obj":"0.9997619,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"441"},{"span":{"begin":16765,"end":16771},"obj":"0.9949635,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"442"},{"span":{"begin":16779,"end":16792},"obj":"0.9996861,experimental_method,cleaner0,2023-07-19T15:32:49Z,MESH:","id":"443"},{"span":{"begin":16796,"end":16811},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"868"},{"span":{"begin":16812,"end":16818},"obj":"0.9971846,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"444"},{"span":{"begin":16830,"end":16837},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"918"},{"span":{"begin":16838,"end":16844},"obj":"0.99816895,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"445"},{"span":{"begin":16868,"end":16874},"obj":"0.9998957,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"446"},{"span":{"begin":16879,"end":16885},"obj":"0.99989843,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"447"},{"span":{"begin":16893,"end":16899},"obj":"0.9886769,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"448"},{"span":{"begin":16911,"end":16917},"obj":"0.9916482,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"449"},{"span":{"begin":16926,"end":16936},"obj":"0.99948066,evidence,cleaner0,2023-07-19T15:32:55Z,DUMMY:","id":"450"},{"span":{"begin":16945,"end":16955},"obj":"protein,PR:,cleaner0,2023-07-19T15:53:22Z","id":"828"},{"span":{"begin":16964,"end":16978},"obj":"0.99942446,complex_assembly,cleaner0,2023-07-19T15:33:06Z,GO:","id":"453"},{"span":{"begin":16996,"end":17007},"obj":"0.99912286,complex_assembly,cleaner0,2023-07-19T15:33:12Z,GO:","id":"454"},{"span":{"begin":17009,"end":17024},"obj":"0.99949425,experimental_method,cleaner0,2023-07-19T15:34:49Z,MESH:","id":"455"},{"span":{"begin":17070,"end":17079},"obj":"0.99952996,evidence,cleaner0,2023-07-19T15:34:46Z,DUMMY:","id":"456"},{"span":{"begin":17083,"end":17101},"obj":"0.9994172,complex_assembly,cleaner0,2023-07-19T15:33:28Z,GO:","id":"457"},{"span":{"begin":17114,"end":17120},"obj":"0.84812504,experimental_method,cleaner0,2023-07-19T15:34:51Z,MESH:","id":"458"},{"span":{"begin":17169,"end":17175},"obj":"0.98904616,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"459"},{"span":{"begin":17176,"end":17183},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"919"},{"span":{"begin":17184,"end":17201},"obj":"0.999605,evidence,cleaner0,2023-07-19T15:34:41Z,DUMMY:","id":"460"},{"span":{"begin":17236,"end":17254},"obj":"0.9969038,complex_assembly,cleaner0,2023-07-19T15:33:29Z,GO:","id":"461"},{"span":{"begin":17255,"end":17264},"obj":"0.99960536,evidence,cleaner0,2023-07-19T15:34:38Z,DUMMY:","id":"462"},{"span":{"begin":17299,"end":17307},"obj":"0.99971807,structure_element,cleaner0,2023-07-19T15:34:34Z,SO:","id":"463"},{"span":{"begin":17317,"end":17337},"obj":"complex_assembly,GO:,cleaner0,2023-07-19T15:34:27Z","id":"822"},{"span":{"begin":17338,"end":17347},"obj":"0.9993129,evidence,cleaner0,2023-07-19T15:34:43Z,DUMMY:","id":"467"},{"span":{"begin":17355,"end":17363},"obj":"0.99970734,structure_element,cleaner0,2023-07-19T15:34:33Z,SO:","id":"468"},{"span":{"begin":17405,"end":17409},"obj":"0.99849415,residue_name_number,cleaner0,2023-07-19T15:33:49Z,DUMMY:","id":"469"},{"span":{"begin":17431,"end":17446},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"869"},{"span":{"begin":17447,"end":17453},"obj":"0.9986848,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"470"},{"span":{"begin":17459,"end":17465},"obj":"0.9999069,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"471"},{"span":{"begin":17499,"end":17505},"obj":"0.9960114,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"472"},{"span":{"begin":17519,"end":17538},"obj":"0.99961,site,cleaner0,2023-07-19T15:34:59Z,SO:","id":"473"},{"span":{"begin":17542,"end":17546},"obj":"0.99980706,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"474"},{"span":{"begin":17558,"end":17567},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T15:35:15Z","id":"823"},{"span":{"begin":17594,"end":17600},"obj":"0.9943234,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"476"},{"span":{"begin":17625,"end":17636},"obj":"0.998801,experimental_method,cleaner0,2023-07-19T15:53:32Z,MESH:","id":"477"},{"span":{"begin":17645,"end":17649},"obj":"0.99946564,evidence,cleaner0,2023-07-19T15:35:28Z,DUMMY:","id":"478"},{"span":{"begin":17717,"end":17723},"obj":"0.9960063,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"479"},{"span":{"begin":17728,"end":17734},"obj":"0.99231964,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"480"},{"span":{"begin":17794,"end":17800},"obj":"0.9998167,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"482"},{"span":{"begin":17805,"end":17811},"obj":"0.9998622,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"483"},{"span":{"begin":17827,"end":17849},"obj":"0.9993809,evidence,cleaner0,2023-07-19T15:35:33Z,DUMMY:","id":"484"},{"span":{"begin":17863,"end":17879},"obj":"0.9976566,evidence,cleaner0,2023-07-19T15:35:38Z,DUMMY:","id":"485"},{"span":{"begin":17884,"end":17890},"obj":"0.99972934,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"486"},{"span":{"begin":17964,"end":17991},"obj":"0.99948543,experimental_method,cleaner0,2023-07-19T15:35:43Z,MESH:","id":"487"},{"span":{"begin":18005,"end":18012},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"921"},{"span":{"begin":18071,"end":18077},"obj":"0.99954575,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"488"},{"span":{"begin":18110,"end":18137},"obj":"0.9995101,experimental_method,cleaner0,2023-07-19T15:35:43Z,MESH:","id":"489"},{"span":{"begin":18151,"end":18158},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"922"},{"span":{"begin":18293,"end":18299},"obj":"0.99965596,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"490"},{"span":{"begin":18317,"end":18338},"obj":"0.99805737,protein_state,cleaner0,2023-07-19T16:01:14Z,DUMMY:","id":"491"},{"span":{"begin":18339,"end":18348},"obj":"0.9991708,evidence,cleaner0,2023-07-19T15:35:59Z,DUMMY:","id":"492"},{"span":{"begin":18388,"end":18394},"obj":"0.999673,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"494"},{"span":{"begin":18407,"end":18414},"obj":"0.9903914,protein_state,cleaner0,2023-07-19T16:01:37Z,DUMMY:","id":"495"},{"span":{"begin":18419,"end":18434},"obj":"0.9016677,protein_state,cleaner0,2023-07-19T16:01:19Z,DUMMY:","id":"496"},{"span":{"begin":18435,"end":18445},"obj":"0.9906707,evidence,cleaner0,2023-07-19T15:36:01Z,DUMMY:","id":"497"},{"span":{"begin":18511,"end":18524},"obj":"0.99437535,chemical,cleaner0,2023-07-19T15:13:56Z,CHEBI:","id":"498"},{"span":{"begin":18540,"end":18546},"obj":"0.99684626,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"499"},{"span":{"begin":18552,"end":18562},"obj":"0.8270343,experimental_method,cleaner0,2023-07-19T15:53:36Z,MESH:","id":"500"},{"span":{"begin":18574,"end":18584},"obj":"0.74309015,evidence,cleaner0,2023-07-19T15:36:04Z,DUMMY:","id":"501"},{"span":{"begin":18600,"end":18607},"obj":"0.88217115,protein_state,cleaner0,2023-07-19T16:01:38Z,DUMMY:","id":"502"},{"span":{"begin":18637,"end":18643},"obj":"0.53165466,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"503"},{"span":{"begin":18644,"end":18653},"obj":"0.9989053,evidence,cleaner0,2023-07-19T15:36:06Z,DUMMY:","id":"504"},{"span":{"begin":18676,"end":18682},"obj":"0.80424184,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"505"},{"span":{"begin":18691,"end":18697},"obj":"0.9997873,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"506"},{"span":{"begin":18703,"end":18709},"obj":"0.9998599,residue_name_number,cleaner0,2023-07-19T15:19:02Z,DUMMY:","id":"507"},{"span":{"begin":18717,"end":18726},"obj":"0.99969506,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"508"},{"span":{"begin":18743,"end":18749},"obj":"0.9998171,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"509"},{"span":{"begin":18795,"end":18799},"obj":"0.9997954,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"510"},{"span":{"begin":18820,"end":18826},"obj":"0.9986603,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"511"},{"span":{"begin":18831,"end":18846},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"871"},{"span":{"begin":18847,"end":18855},"obj":"0.9993025,chemical,cleaner0,2023-07-19T15:36:21Z,CHEBI:","id":"512"},{"span":{"begin":18866,"end":18875},"obj":"0.9996755,protein_state,cleaner0,2023-07-19T15:36:15Z,DUMMY:","id":"513"},{"span":{"begin":18909,"end":18913},"obj":"0.6189321,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"514"},{"span":{"begin":18931,"end":18951},"obj":"0.99943864,evidence,cleaner0,2023-07-19T15:36:12Z,DUMMY:","id":"515"},{"span":{"begin":18959,"end":18966},"obj":"0.99830246,experimental_method,cleaner0,2023-07-19T15:36:34Z,MESH:","id":"516"},{"span":{"begin":18970,"end":18974},"obj":"0.99475783,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"517"},{"span":{"begin":18975,"end":18985},"obj":"0.9991398,evidence,cleaner0,2023-07-19T15:36:36Z,DUMMY:","id":"518"},{"span":{"begin":18986,"end":18994},"obj":"0.9994433,protein_state,cleaner0,2023-07-19T15:24:12Z,DUMMY:","id":"519"},{"span":{"begin":18995,"end":19001},"obj":"0.9967662,chemical,cleaner0,2023-07-19T16:06:49Z,CHEBI:","id":"520"},{"span":{"begin":19011,"end":19017},"obj":"0.9978752,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"521"},{"span":{"begin":19029,"end":19037},"obj":"0.96408117,chemical,cleaner0,2023-07-19T15:36:22Z,CHEBI:","id":"522"},{"span":{"begin":19048,"end":19055},"obj":"0.99945694,experimental_method,cleaner0,2023-07-19T15:36:42Z,MESH:","id":"523"},{"span":{"begin":19059,"end":19063},"obj":"0.99989235,residue_name_number,cleaner0,2023-07-19T15:50:13Z,DUMMY:","id":"524"},{"span":{"begin":19067,"end":19071},"obj":"0.99910957,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"525"},{"span":{"begin":19072,"end":19081},"obj":"0.9986027,evidence,cleaner0,2023-07-19T15:36:44Z,DUMMY:","id":"526"},{"span":{"begin":19082,"end":19088},"obj":"0.997511,chemical,cleaner0,2023-07-19T16:07:00Z,CHEBI:","id":"527"},{"span":{"begin":19098,"end":19104},"obj":"0.99866104,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"528"},{"span":{"begin":19113,"end":19120},"obj":"0.9995783,chemical,cleaner0,2023-07-19T15:36:55Z,CHEBI:","id":"529"},{"span":{"begin":19208,"end":19228},"obj":"0.9994807,evidence,cleaner0,2023-07-19T15:37:12Z,DUMMY:","id":"530"},{"span":{"begin":19232,"end":19236},"obj":"0.99975437,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"531"},{"span":{"begin":19242,"end":19250},"obj":"0.9983985,chemical,cleaner0,2023-07-19T15:36:22Z,CHEBI:","id":"532"},{"span":{"begin":19272,"end":19287},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"872"},{"span":{"begin":19291,"end":19295},"obj":"0.9997485,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"533"},{"span":{"begin":19297,"end":19301},"obj":"0.9804152,evidence,cleaner0,2023-07-19T15:51:33Z,DUMMY:","id":"534"},{"span":{"begin":19316,"end":19344},"obj":"0.99956346,experimental_method,cleaner0,2023-07-19T15:37:06Z,MESH:","id":"535"},{"span":{"begin":19352,"end":19356},"obj":"0.9948265,evidence,cleaner0,2023-07-19T15:51:37Z,DUMMY:","id":"536"},{"span":{"begin":19372,"end":19382},"obj":"0.99950325,experimental_method,cleaner0,2023-07-19T15:15:19Z,MESH:","id":"537"},{"span":{"begin":19427,"end":19436},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T15:37:44Z","id":"824"},{"span":{"begin":19465,"end":19474},"obj":"0.63860226,evidence,cleaner0,2023-07-19T15:51:41Z,DUMMY:","id":"539"},{"span":{"begin":19478,"end":19484},"obj":"0.9829714,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"540"},{"span":{"begin":19519,"end":19530},"obj":"0.9992175,experimental_method,cleaner0,2023-07-19T15:37:15Z,MESH:","id":"541"},{"span":{"begin":19539,"end":19543},"obj":"0.99965835,evidence,cleaner0,2023-07-19T15:35:28Z,DUMMY:","id":"542"},{"span":{"begin":19586,"end":19604},"obj":"0.99770904,chemical,cleaner0,2023-07-19T15:37:28Z,CHEBI:","id":"543"},{"span":{"begin":19614,"end":19622},"obj":"0.9959305,chemical,cleaner0,2023-07-19T15:36:22Z,CHEBI:","id":"544"},{"span":{"begin":19647,"end":19663},"obj":"0.9994836,evidence,cleaner0,2023-07-19T15:25:47Z,DUMMY:","id":"545"},{"span":{"begin":19705,"end":19711},"obj":"0.99987984,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"546"},{"span":{"begin":19733,"end":19739},"obj":"0.9998841,residue_name_number,cleaner0,2023-07-19T15:19:02Z,DUMMY:","id":"547"},{"span":{"begin":19747,"end":19751},"obj":"0.9995697,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"548"},{"span":{"begin":19752,"end":19758},"obj":"0.8003477,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"549"},{"span":{"begin":19759,"end":19766},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"927"},{"span":{"begin":19767,"end":19776},"obj":"0.9993617,evidence,cleaner0,2023-07-19T15:37:20Z,DUMMY:","id":"550"},{"span":{"begin":19808,"end":19814},"obj":"0.99987173,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"551"},{"span":{"begin":19845,"end":19853},"obj":"0.9912252,chemical,cleaner0,2023-07-19T15:36:22Z,CHEBI:","id":"552"},{"span":{"begin":19854,"end":19858},"obj":"0.99891305,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"553"},{"span":{"begin":19859,"end":19868},"obj":"0.99936765,evidence,cleaner0,2023-07-19T15:37:23Z,DUMMY:","id":"554"},{"span":{"begin":19883,"end":19889},"obj":"0.86961484,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"555"},{"span":{"begin":19987,"end":19995},"obj":"0.99782795,chemical,cleaner0,2023-07-19T15:36:22Z,CHEBI:","id":"556"},{"span":{"begin":20008,"end":20014},"obj":"0.9925011,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"557"},{"span":{"begin":20022,"end":20032},"obj":"0.99927664,experimental_method,cleaner0,2023-07-19T15:15:19Z,MESH:","id":"558"},{"span":{"begin":20050,"end":20071},"obj":"0.9995247,evidence,cleaner0,2023-07-19T15:37:57Z,DUMMY:","id":"559"},{"span":{"begin":20075,"end":20079},"obj":"0.9997024,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"560"},{"span":{"begin":20148,"end":20154},"obj":"0.9989466,protein_state,cleaner0,2023-07-19T15:37:52Z,DUMMY:","id":"561"},{"span":{"begin":20186,"end":20195},"obj":"0.9995504,protein_state,cleaner0,2023-07-19T15:37:54Z,DUMMY:","id":"562"},{"span":{"begin":20219,"end":20225},"obj":"0.9995369,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"563"},{"span":{"begin":20230,"end":20240},"obj":"0.9996209,chemical,cleaner0,2023-07-19T16:07:05Z,CHEBI:","id":"564"},{"span":{"begin":20246,"end":20261},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"873"},{"span":{"begin":20326,"end":20332},"obj":"0.99989784,residue_name_number,cleaner0,2023-07-19T15:28:25Z,DUMMY:","id":"565"},{"span":{"begin":20347,"end":20353},"obj":"0.99989426,residue_name_number,cleaner0,2023-07-19T15:18:57Z,DUMMY:","id":"566"},{"span":{"begin":20366,"end":20381},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"874"},{"span":{"begin":20382,"end":20398},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"946"},{"span":{"begin":20410,"end":20416},"obj":"0.9999031,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"567"},{"span":{"begin":20450,"end":20457},"obj":"0.99489343,protein_state,cleaner0,2023-07-19T16:01:38Z,DUMMY:","id":"568"},{"span":{"begin":20474,"end":20478},"obj":"0.9996356,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"569"},{"span":{"begin":20480,"end":20486},"obj":"0.9995697,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"570"},{"span":{"begin":20520,"end":20526},"obj":"0.9999018,residue_name_number,cleaner0,2023-07-19T15:28:25Z,DUMMY:","id":"571"},{"span":{"begin":20534,"end":20540},"obj":"0.9998988,residue_name_number,cleaner0,2023-07-19T15:18:57Z,DUMMY:","id":"572"},{"span":{"begin":20553,"end":20566},"obj":"bond_interaction,MESH:,melaniev@ebi.ac.uk,2023-07-28T14:18:02Z","id":"938"},{"span":{"begin":20572,"end":20578},"obj":"0.9999014,residue_name_number,cleaner0,2023-07-19T15:25:24Z,DUMMY:","id":"573"},{"span":{"begin":20685,"end":20700},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"875"},{"span":{"begin":20701,"end":20719},"obj":"0.9996216,evidence,cleaner0,2023-07-19T15:38:08Z,DUMMY:","id":"574"},{"span":{"begin":20738,"end":20744},"obj":"0.9999008,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"575"},{"span":{"begin":20802,"end":20806},"obj":"0.9991548,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"576"},{"span":{"begin":20807,"end":20814},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"931"},{"span":{"begin":20815,"end":20825},"obj":"0.7199689,evidence,cleaner0,2023-07-19T15:38:11Z,DUMMY:","id":"577"},{"span":{"begin":20831,"end":20837},"obj":"0.99945503,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"578"},{"span":{"begin":20875,"end":20893},"obj":"0.99954826,chemical,cleaner0,2023-07-19T15:38:05Z,CHEBI:","id":"579"},{"span":{"begin":20996,"end":21002},"obj":"0.9948939,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"580"},{"span":{"begin":21025,"end":21029},"obj":"0.9997609,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"581"},{"span":{"begin":21035,"end":21039},"obj":"0.99983096,protein,cleaner0,2023-07-19T15:16:02Z,PR:","id":"582"},{"span":{"begin":21044,"end":21048},"obj":"0.99983597,protein,cleaner0,2023-07-19T15:16:06Z,PR:","id":"583"},{"span":{"begin":21054,"end":21082},"obj":"0.9995607,experimental_method,cleaner0,2023-07-19T15:38:17Z,MESH:","id":"584"},{"span":{"begin":21094,"end":21109},"obj":"0.9994817,experimental_method,cleaner0,2023-07-19T15:38:20Z,MESH:","id":"585"},{"span":{"begin":21134,"end":21140},"obj":"0.9978909,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"586"},{"span":{"begin":21148,"end":21152},"obj":"0.9998468,protein,cleaner0,2023-07-19T15:16:02Z,PR:","id":"587"},{"span":{"begin":21157,"end":21161},"obj":"0.9998485,protein,cleaner0,2023-07-19T15:16:06Z,PR:","id":"588"},{"span":{"begin":21165,"end":21169},"obj":"0.98739153,protein,cleaner0,2023-07-19T15:57:30Z,PR:","id":"589"},{"span":{"begin":21304,"end":21311},"obj":"0.9992525,experimental_method,cleaner0,2023-07-19T15:38:33Z,MESH:","id":"595"},{"span":{"begin":21315,"end":21319},"obj":"0.99982053,protein,cleaner0,2023-07-19T15:16:02Z,PR:","id":"596"},{"span":{"begin":21330,"end":21331},"obj":"0.9997744,protein,cleaner0,2023-07-19T15:38:36Z,PR:","id":"597"},{"span":{"begin":21343,"end":21344},"obj":"0.999747,protein,cleaner0,2023-07-19T15:38:39Z,PR:","id":"598"},{"span":{"begin":21386,"end":21392},"obj":"0.9998907,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"599"},{"span":{"begin":21445,"end":21458},"obj":"chemical,CHEBI:,cleaner0,2023-07-19T15:13:56Z","id":"784"},{"span":{"begin":21474,"end":21480},"obj":"0.99398804,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"600"},{"span":{"begin":21546,"end":21552},"obj":"0.99780947,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"601"},{"span":{"begin":21555,"end":21578},"obj":"0.99894136,experimental_method,cleaner0,2023-07-19T15:39:38Z,MESH:","id":"602"},{"span":{"begin":21605,"end":21627},"obj":"0.9995373,structure_element,cleaner0,2023-07-19T15:39:40Z,SO:","id":"603"},{"span":{"begin":21631,"end":21634},"obj":"0.9841285,protein_type,cleaner0,2023-07-19T15:14:21Z,MESH:","id":"604"},{"span":{"begin":21635,"end":21636},"obj":"0.9995415,protein,cleaner0,2023-07-19T15:39:27Z,PR:","id":"605"},{"span":{"begin":21638,"end":21639},"obj":"0.9996561,protein,cleaner0,2023-07-19T15:39:30Z,PR:","id":"606"},{"span":{"begin":21644,"end":21645},"obj":"0.9997303,protein,cleaner0,2023-07-19T15:39:33Z,PR:","id":"607"},{"span":{"begin":21651,"end":21659},"obj":"0.774799,experimental_method,cleaner0,2023-07-19T15:39:35Z,MESH:","id":"608"},{"span":{"begin":21664,"end":21682},"obj":"0.99931574,structure_element,cleaner0,2023-07-19T15:16:53Z,SO:","id":"609"},{"span":{"begin":21690,"end":21712},"obj":"0.96916354,protein_type,cleaner0,2023-07-19T15:39:49Z,MESH:","id":"610"},{"span":{"begin":21713,"end":21717},"obj":"0.8299078,protein,cleaner0,2023-07-19T15:39:52Z,PR:","id":"611"},{"span":{"begin":21723,"end":21726},"obj":"protein_type,MESH:,cleaner0,2023-07-19T15:14:21Z","id":"798"},{"span":{"begin":21727,"end":21731},"obj":"protein,PR:,cleaner0,2023-07-19T15:57:30Z","id":"846"},{"span":{"begin":21829,"end":21833},"obj":"protein,PR:,cleaner0,2023-07-19T15:57:30Z","id":"847"},{"span":{"begin":21844,"end":21850},"obj":"0.99855095,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"614"},{"span":{"begin":21924,"end":21928},"obj":"protein,PR:,cleaner0,2023-07-19T15:12:45Z","id":"780"},{"span":{"begin":21929,"end":21933},"obj":"protein,PR:,cleaner0,2023-07-19T15:57:30Z","id":"848"},{"span":{"begin":21957,"end":21961},"obj":"0.99954826,evidence,cleaner0,2023-07-19T15:52:08Z,DUMMY:","id":"616"},{"span":{"begin":22037,"end":22041},"obj":"0.34280136,protein,cleaner0,2023-07-19T15:57:30Z,PR:","id":"617"},{"span":{"begin":22055,"end":22058},"obj":"0.9998186,structure_element,cleaner0,2023-07-19T15:17:06Z,SO:","id":"618"},{"span":{"begin":22062,"end":22065},"obj":"0.6574821,protein_type,cleaner0,2023-07-19T15:14:21Z,MESH:","id":"619"},{"span":{"begin":22066,"end":22067},"obj":"0.9995084,protein,cleaner0,2023-07-19T15:40:06Z,PR:","id":"620"},{"span":{"begin":22071,"end":22072},"obj":"0.9996867,protein,cleaner0,2023-07-19T15:40:09Z,PR:","id":"621"},{"span":{"begin":22102,"end":22105},"obj":"0.99981755,site,cleaner0,2023-07-19T15:18:14Z,SO:","id":"622"},{"span":{"begin":22109,"end":22113},"obj":"0.9994504,protein_type,cleaner0,2023-07-19T15:16:33Z,MESH:","id":"623"},{"span":{"begin":22189,"end":22195},"obj":"0.99703026,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"624"},{"span":{"begin":22205,"end":22211},"obj":"0.99989223,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"625"},{"span":{"begin":22218,"end":22225},"obj":"0.9991722,residue_name,cleaner0,2023-07-19T15:40:17Z,SO:","id":"626"},{"span":{"begin":22234,"end":22238},"obj":"0.9998022,protein,cleaner0,2023-07-19T15:16:02Z,PR:","id":"627"},{"span":{"begin":22243,"end":22244},"obj":"0.9997577,protein,cleaner0,2023-07-19T15:56:20Z,PR:","id":"628"},{"span":{"begin":22275,"end":22281},"obj":"0.99747974,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"629"},{"span":{"begin":22311,"end":22318},"obj":"0.99865365,residue_name,cleaner0,2023-07-19T15:40:17Z,SO:","id":"630"},{"span":{"begin":22333,"end":22337},"obj":"0.9997924,protein,cleaner0,2023-07-19T15:16:02Z,PR:","id":"631"},{"span":{"begin":22342,"end":22343},"obj":"0.99976355,protein,cleaner0,2023-07-19T15:40:25Z,PR:","id":"632"},{"span":{"begin":22370,"end":22383},"obj":"0.9991916,residue_name,cleaner0,2023-07-19T15:40:21Z,SO:","id":"633"},{"span":{"begin":22391,"end":22400},"obj":"0.9997171,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"634"},{"span":{"begin":22434,"end":22440},"obj":"0.99989223,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"635"},{"span":{"begin":22458,"end":22462},"obj":"0.9997229,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"636"},{"span":{"begin":22512,"end":22516},"obj":"0.9998173,protein,cleaner0,2023-07-19T15:16:02Z,PR:","id":"637"},{"span":{"begin":22530,"end":22543},"obj":"0.9992132,residue_name,cleaner0,2023-07-19T15:40:21Z,SO:","id":"638"},{"span":{"begin":22560,"end":22563},"obj":"0.9998124,site,cleaner0,2023-07-19T15:18:14Z,SO:","id":"639"},{"span":{"begin":22572,"end":22576},"obj":"0.9997999,protein,cleaner0,2023-07-19T15:16:06Z,PR:","id":"640"},{"span":{"begin":22581,"end":22582},"obj":"0.9997799,protein,cleaner0,2023-07-19T15:40:28Z,PR:","id":"641"},{"span":{"begin":22590,"end":22597},"obj":"0.99925333,residue_name,cleaner0,2023-07-19T15:40:17Z,SO:","id":"642"},{"span":{"begin":22658,"end":22671},"obj":"0.99922276,residue_name,cleaner0,2023-07-19T15:40:21Z,SO:","id":"643"},{"span":{"begin":22688,"end":22691},"obj":"0.99981564,site,cleaner0,2023-07-19T15:18:14Z,SO:","id":"644"},{"span":{"begin":22695,"end":22699},"obj":"0.999821,protein,cleaner0,2023-07-19T15:16:02Z,PR:","id":"645"},{"span":{"begin":22712,"end":22734},"obj":"0.99927276,chemical,cleaner0,2023-07-19T15:40:31Z,CHEBI:","id":"646"},{"span":{"begin":22750,"end":22756},"obj":"0.99807584,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"647"},{"span":{"begin":22825,"end":22829},"obj":"0.999803,protein,cleaner0,2023-07-19T15:16:02Z,PR:","id":"648"},{"span":{"begin":22835,"end":22836},"obj":"0.999731,protein,cleaner0,2023-07-19T15:56:26Z,PR:","id":"649"},{"span":{"begin":22959,"end":22972},"obj":"0.9997615,chemical,cleaner0,2023-07-19T15:13:56Z,CHEBI:","id":"650"},{"span":{"begin":23028,"end":23032},"obj":"0.9997459,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"651"},{"span":{"begin":23038,"end":23054},"obj":"0.99949485,experimental_method,cleaner0,2023-07-19T15:14:47Z,MESH:","id":"652"},{"span":{"begin":23062,"end":23081},"obj":"0.9995538,experimental_method,cleaner0,2023-07-19T15:40:50Z,MESH:","id":"653"},{"span":{"begin":23137,"end":23146},"obj":"0.9997312,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"654"},{"span":{"begin":23150,"end":23154},"obj":"0.99975103,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"655"},{"span":{"begin":23164,"end":23179},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:20Z","id":"876"},{"span":{"begin":23180,"end":23186},"obj":"0.9993443,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"656"},{"span":{"begin":23202,"end":23206},"obj":"0.99973184,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"657"},{"span":{"begin":23207,"end":23228},"obj":"0.99941427,evidence,cleaner0,2023-07-19T15:40:53Z,DUMMY:","id":"658"},{"span":{"begin":23328,"end":23335},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"933"},{"span":{"begin":23337,"end":23343},"obj":"0.99953425,chemical,cleaner0,2023-07-19T15:14:02Z,CHEBI:","id":"659"},{"span":{"begin":23365,"end":23371},"obj":"0.9995059,chemical,cleaner0,2023-07-19T15:14:09Z,CHEBI:","id":"660"},{"span":{"begin":23441,"end":23445},"obj":"0.99942756,protein,cleaner0,2023-07-19T15:12:45Z,PR:","id":"661"},{"span":{"begin":23501,"end":23507},"obj":"0.9998945,residue_name_number,cleaner0,2023-07-19T15:15:13Z,DUMMY:","id":"662"},{"span":{"begin":23527,"end":23534},"obj":"protein_state,DUMMY:,cleaner0,2023-07-19T16:01:38Z","id":"934"},{"span":{"begin":23555,"end":23564},"obj":"0.99972713,structure_element,cleaner0,2023-07-19T15:14:26Z,SO:","id":"663"}],"relations":[]}]