bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the products of genes encompassed by the theoretically predicted pathogenicity islands of Mycobacterium tuberculosis and Mycobacterium bovis
Authors: Zubrzycki Igor Z. 
Published: January 2004

AbstractSequencing of the genomes of Mycobacterium tuberculosis and Mycobacterium bovis provides a unique opportunity to study the biology of these pathogens on the genomic level. The computational detection of anomalous gene clusters such as those encompassed by pathogenicity islands allows for a narrowing of the study into well‐defined groups of genes. Pathogenicity islands of M. tuberculosis (strains H37Rv and CDC1551) as well as M. bovis genomes comprise a group of genes encoding proteins that have been shown to be of immunological importance. The cross‐genomic comparison (M. tuberculosis vs M. bovis) resulted in the elucidation of unique proteins in M. tuberculosis. These proteins may play a significant role in the host recognition process. Proteins 2004; 54:000–000. © 2003 Wiley‐Liss, Inc.
A pharmacophore docking algorithm and its application to the cross‐docking of 18 HIV‐NNRTI's in their binding pockets
Authors: Daeyaert Frits , de Jonge Marc , Heeres Jan , Koymans Luc , Lewi Paul , Vinkers Maarten H. , Janssen Paul A.J. 
Published: January 2004

AbstractThe docking of small molecules into the binding site of a target protein is an important but difficult step in structure‐based drug design. The performance of a docking algorithm is usually evaluated by re‐docking ligands into their native binding sites. We have explored the cross‐docking of 18 HIV‐NNRTIs (non‐nucleoside inhibitors of HIV reverse transcriptase) of which the ligand–protein structure has been determined: each of the 18 ligands was docked into each of the 18 binding sites. The docking algorithms studied are an energy‐based simulated annealing algorithm and a novel pharmacophore docking algorithm. It turns out that the energy‐based docking of the ligands into non‐native pockets is far less successful than the docking into their native pockets. The results can be improved by using explicit pharmacophore information, and by docking a ligand into a panel of protein structures and selecting the ligand–proteincombination with the lowest interaction energy as the final result. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Efficient methods for filtering and ranking fragments for the prediction of structurally variable regions in proteins
Authors: Heuser Philipp , Wohlfahrt Gerd , Schomburg Dietmar 
Published: January 2004

AbstractThe prediction of protein 3D structures close to insertions and deletions or, more generally, loop prediction, is still one of the major challenges in homology modeling projects. In this article, we developed ranking criteria and selection filters to improve knowledge‐based loop predictions. These criteria were developed and optimized for a test data set containing 678 insertions and deletions. The examples are, in principle, predictable from the used loop database with an RMSD < 1 Å and represent realistic modeling situations. Four noncorrelated criteria for the selection of fragments are evaluated. A fast prefilter compares the distance between the anchor groups in the template protein with the stems of the fragments. The RMSD of the anchor groups is used for fitting and ranking of the selected loop candidates. After fitting, repulsive close contacts of loop candidates with the template protein are used for filtering, and fragments with backbone torsion angles, which are unfavorable according to a knowledge‐based potential, are eliminated. By the combined application of these filter criteria to the test set, it was possible to increase the percentage of predictions with a global RMSD < 1 Å to over 50% among the first five ranks, with average global RMSD values for the first rank candidate that are between 1.3 and 2.2 Å for different loop lengths. Compared to other examples described in the literature, our large numbers of test cases are not self‐predictions, where loops are placed in a protein after a peptide loop has been cut out, but are attempts to predict structural changes that occur in evolution when a protein is affected by insertions and deletions. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Three acidic residues are at the active site of a β‐propeller architecture in glycoside hydrolase families 32, 43, 62, and 68
Authors: Pons Tirso , Naumoff Daniil G. , Martínez‐Fleites Carlos , Hernández Lázaro 
Published: January 2004

AbstractMultiple‐sequence alignment of glycoside hydrolase (GH) families 32, 43, 62, and 68 revealed three conserved blocks, each containing an acidic residue at an equivalent position in all the enzymes. A detailed analysis of the site‐directed mutations so far performed on invertases (GH32), arabinanases (GH43), and bacterial fructosyltransferases (GH68) indicated a direct implication of the conserved residues Asp/Glu (block I), Asp (block II), and Glu (block III) in substrate binding and hydrolysis. These residues are close in space in the 5‐bladed β‐propeller fold determined for Cellvibrio japonicus α‐L‐arabinanase Arb43A [Nurizzo et al., Nat Struct Biol 2002;9:665–668] and Bacillus subtilis endo‐1,5‐α‐L‐arabinanase. A sequence–structure compatibility search using 3D‐PSSM, mGenTHREADER, INBGU, and SAM‐T02 programs predicted indistinctly the 5‐bladed β‐propeller fold of Arb43A and the 6‐bladed β‐propeller fold of sialidase/neuraminidase (GH33, GH34, and GH83) as the most reliable topologies for GH families 32, 62, and 68. We conclude that the identified acidic residues are located at the active site of a β‐propeller architecture in GH32, GH43, GH62, and GH68, operating with a canonical reaction mechanism of either inversion (GH43 and likely GH62) or retention (GH32 and GH68) of the anomeric configuration. Also, we propose that the β‐propeller architecture accommodates distinct binding sites for the acceptor saccharide in glycosyl transfer reaction. Proteins 2004. © 2003 Wiley‐Liss, Inc.
Solution structure of the highly acidic protein HI1450 from Haemophilus influenzae, a putative double‐stranded DNA mimic
Authors: Parsons Lisa M. , Yeh Deok Cheon , Orban John 
Published: January 2004

AbstractThe solution structure of the acidic protein HI1450 from Haemophilus influenzae has been determined by NMR spectroscopy. HI1450 has homologues in ten other bacterial species including Escherichia coli, Vibrio cholerae, and Yersinia pestis but there are no functional assignments for any members of the family. Thirty‐one of the amino acids in this 107‐residue protein are aspartates or glutamates, contributing to an unusually low pI of 3.72. The secondary structure elements are arranged in an α‐α‐β‐β‐β‐β order with the two alpha helices packed against the same side of an anti‐parallel four‐stranded beta meander. Two large loops, one between β1 and β2 and the other between β2 and β3 bend almost perpendicularly across the β‐strands in opposite directions on the non‐helical side of the β‐sheet to form a conserved hydrophobic cavity. The HI1450 structure has some similarities to the structure of the double‐stranded DNA (dsDNA) mimic uracil DNA glycosylase inhibitor (Ugi) including the distribution of surface charges and the position of the hydrophobic cavity. Based on these similarities, as well as having a comparable molecular surface to dsDNA, we propose that HI1450 may function as a dsDNA mimic in order to inhibit or regulate an as yet unidentified dsDNA binding protein. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Predicting peptide binding to MHC pockets via molecular modeling, implicit solvation, and global optimization
Authors: Schafroth Heather D. , Floudas Christodoulos A. 
Published: January 2004

AbstractDevelopment of a computational prediction method based on molecular modeling, global optimization, and implicit solvation has produced accurate structure and relative binding affinity predictions for peptide amino acids binding to five pockets of the MHC molecule HLA‐DRB1*0101. Because peptide binding to MHC molecules is essential to many immune responses, development of such a method for understanding and predicting the forces that drive binding is crucial for pharmaceutical design and disease treatment. Underlying the development of this prediction method are two hypotheses. The first is that pockets formed by the peptide binding groove of MHC molecules are independent, separating the prediction of peptide amino acids that bind within individual pockets from those that bind between pockets. The second hypothesis is that the native state of a system composed of an amino acid bound to a protein pocket corresponds to the system's lowest free energy. The prediction method developed from these hypotheses uses atomistic‐level modeling, deterministic global optimization, and three methods of implicit solvation: solvent‐accessible area, solvent‐accessible volume, and Poisson–Boltzmann electrostatics. The method predicts relative binding affinities of peptide amino acids for pockets of HLA‐DRB1*0101 by determining computationally an amino acid's global minimum energy conformation. Prediction results from the method are in agreement with X‐ray crystallography data and experimental binding assays. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Comparison of backbone dynamics of monomeric and domain‐swapped stefin A
Authors: Japelj Boštjan , Waltho Jonathan P. , Jerala Roman 
Published: January 2004

AbstractThree‐dimensional domain swapping has been observed in increasing number of proteins and has been implicated in the initial stages of protein aggregation, including that of the cystatins. Stefin A folds as a monomer under native conditions, while under some denaturing conditions domain‐swapped dimer is formed. We have determined the backbone dynamics of the monomeric and domain‐swapped dimeric forms of stefin A by 15N relaxation using a model‐free approach. The overall correlation times of the molecules were determined to be 4.6 ± 0.1 ns and 9.2 ± 0.2 ns for the monomer and the dimer, respectively. In the monomer, decreased order parameters indicate an increased mobility for the N‐terminal trunk, the first and the second binding loops. At the opposite side of the molecule, the loop connecting the α‐helix with strand B, the beginning of strand B and the loop connecting strands C and D show increased localized mobility. In the domain‐swapped dimer, a distinctive feature of the structure is the concatenation of strands B and C into a single long β‐strand. The newly formed linker region between strands B and C, which substitutes for the first binding loop in the monomer, has order parameters typical for the remainder of the β‐strands. Thus, the interaction between subunits that occurs on domain‐swapping has consequences for the dynamics of the protein at long‐range from the site of conformational change, where an increased rigidity in the newly formed linker region is accompanied by an increased mobility of loops remote from that site. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Characterization of a thrombomodulin binding site on protein C and its comparison to an activated protein C binding site for factor Va
Authors: Gale Andrew J. , Griffin John H. 
Published: January 2004

AbstractActivation of the anticoagulant human plasma serine protease zymogen, protein C, by a complex of thrombin and the membrane protein, thrombomodulin, generates activated protein C, a physiologic anti‐thrombotic, anti‐inflammatory and anti‐apoptotic agent. Alanine‐scanning site‐directed mutagenesis of residues in five surface loops of an extensive basic surface on protein C was used to identify residues that play essential roles in its activation by the thrombin‐thrombomodulin complex. Twenty‐three residues in the protein C protease domain were mutated to alanine, singly, in pairs or in triple mutation combinations, and mutants were characterized for their effectiveness as substrates of the thrombin‐thrombomodulin complex. Three protein C residues, K192, R229, and R230, in two loops, were identified that provided major contributions to interactions with thrombin‐thrombomodulin, while six residues, S190, K191, K217, K218, W231, and R312, in four loops, appeared to provide minor contributions. These protein C residues delineated a positively charged area on the molecule's surface that largely overlapped the previously characterized factor Va binding site on activated protein C. Thus, the extensive basic surface of protein C and activated protein C provides distinctly different, though significantly overlapping, binding sites for recognition by thrombin‐thrombomodulin and factor Va. Proteins 2004;54:000–000. © 2004 Wiley‐Liss, Inc.
Metal‐Induced reversible structural interconversion of human mitochondrial NAD(P)+‐Dependent malic enzyme
Authors: Kuo Chu‐Wei , Hung Hui‐Chih , Tong Liang , Chang Gu‐Gang 
Published: January 2004

AbstractHuman mitochondrial NAD(P)+‐dependent malic enzyme was strongly inhibited by Lu3+. The X‐ray crystal structures indicated a structural change between the metal‐free and Lu3+‐containing enzymes (Yang Z, Batra R, Floyd DL, Hung HC, Chang GG, Tong L. Biochem Biophys Res Commun 2000;274:440–444). We characterized the reversible slow‐binding mechanism and the structural interconversion between Mn2+‐ and Lu3+‐containing human mitochondrial malic enzymes. When Lu3+ was added, the activity of the human enzyme showed a downward curve over time, similar to that of the pigeon enzyme. The rate of the transformation (kobs) from the initial rate to the steady‐state rate increased hyperbolically with the concentration of Lu3+, suggesting the involvement of an isomerization step. Lu3+ had a much higher affinity for the isomerized form (K*i,Lu (app) = 4.8 μM) than that of the native form (Ki,Lu (app) = 148 μM). When an excess of Mn2+ was added to the Lu3+‐inhibited enzyme, assays of the kinetic activity showed an upward trend, indicating reactivation. This result also indicated that the reactivation was a slow process. Fluorescence quenching experiments confirmed that the Lu3+‐induced isomerization was completely reversible. The dynamic quenching constants for the metal‐free, Mn2+‐containing, and Lu3+‐containing enzyme were 3.08, 3.07, and 3.8 M−1, respectively. When the Lu3+‐containing enzyme was treated with excess Mn2+, the dynamic quenching constant returned to the original value (3.09 M−1). These results indicated that binding of Mn2+ did not induce any conformational change in the enzyme. The open form transformed to the closed form only after substrate binding. Lu3+, on the other hand, transformed the open form into a catalytically inactive form. Excess Mn2+ could replace Lu3+ in the metal binding site and convert the inactive form back into the open form. This reversible process was slow in both directions because of the same but opposite structural change involved. Proteins 2004;54:000–000. © 2004 Wiley‐Liss, Inc.
Monitoring glyphosate residues in transgenic glyphosate‐resistant soybean
Authors: Arregui María C , Lenardón Argelia , Sanchez Daniel , Maitre María I , Scotta Roberto , Enrique Susana 
Published: January 2004

AbstractThe availability of Roundup Ready (RR) varieties of soybean has increased the use of glyphosate for weed control in Argentina. Glyphosate [(N‐phosphonomethyl)glycine] is employed for the eradication of previous crop vegetation and for weed control during the soybean growing cycle. Its action is effective, and low environmental impact has been reported so far. No residues have been observed in soil or water, either of glyphosate or its metabolite, AMPA (aminomethylphosphonic acid). The objective of this work was to monitor glyphosate and AMPA residues in soybean plants and grains in field crops in Santa Fe Province, Argentina. Five sites were monitored in 1997, 1998 and 1999. Individual soybean plants were sampled from emergence to harvest, dried and ground. Analysis consisted in residue extraction with organic solvents and buffers, agitation, centrifugation, clean‐up and HPLC with UV detection. In soybean leaves and stems, glyphosate residues ranged from 1.9 to 4.4 mg kg−1 and from 0.1 to 1.8 mg kg−1 in grains. Higher concentrations were detected when glyphosate was sprayed several times during the crop cycle, and when treatments approached the flowering stage. AMPA residues were also detected in leaves and in grains, indicating metabolism of the herbicide. Copyright © 2003 Society of Chemical Industry
Synthesis and antifungal activity of five classes of diamines
Authors: Ross William F , Walters Dale R , Robins David J 
Published: January 2004

AbstractExamples of five classes of diamines were synthesized and tested for antifungal activity. Two classes, the bis(cyclohexylmethyl)diamines and the bis(benzyl)diamines, were most effective in reducing mycelial growth of the oat leaf stripe pathogen Pyrenophora avenae Ito & Kuribay when used at a concentration of 250 µM. The bis(benzyl)diamine BBD5 and the hydroxypyridylethylamine HPE2 both reduced powdery mildew infection of barley seedlings by greater than 70% when applied as a post‐inoculation spray at 250 µM. Several of the compounds examined, and especially BBD5 and HPE2, reduced the formation of spermidine but greatly increased spermine levels. These changes in P avenae treated with BBD5 and HPE2 were also accompanied by greatly elevated activity of polyamine oxidase. It is suggested that the antifungal activity of these compounds may be related to the accumulation of spermine and specifically to its toxicity. Copyright © 2004 Society of Chemical Industry
Potassium phosphate induces systemic protection in barley to powdery mildew infection
Authors: Mitchell Anne F , Walters Dale R 
Published: January 2004

AbstractIn laboratory tests, treatment of the first leaves of barley (Hordeum vulgare L cv Golden Promise) with potassium phosphate led to significant reduction in infection of the second leaves with the powdery mildew fungus Blumeria graminis f sp hordei Marchal, with a 25 mM treatment giving 89% reduction in infection. Although the optimal interval between phosphate treatment of the first leaves and mildew inoculation of the second leaves was 2 days, significant protection was still obtained if the interval was increased to 12 days. Protection against powdery mildew infection was not as effective when the potassium phosphate was applied as a seed treatment or root drench. Phosphate treatment of the first leaves led to significant increases in activities of phenylalanine ammonia lyase (PAL), peroxidase and lipoxygenase in second leaves. Enzyme activities, especially PAL and peroxidase, were increased further when second leaves of phosphate‐treated plants were inoculated with powdery mildew. Phosphate treatment of the first leaves did not adversely affect plant growth and, in a field trial, 25 mM potassium phosphate provided 70% control of mildew and gave a small increase in grain yield. Copyright © 2004 Society of Chemical Industry
Occurrence of barley yellow dwarf virus in autumn‐sown cereal crops in the United Kingdom in relation to field characteristics
Authors: Foster Garth N , Blake Shona , Tones Steve J , Barker Ian , Harrington Richard 
Published: January 2004

AbstractThe incidence of barley yellow dwarf virus and of its aphid vectors was surveyed in untreated parts of autumn‐sown cereal crops, mainly wheat and barley, in the United Kingdom in 1995–8. The incidence of virus in the spring was related to the incidence of aphids in the preceding autumn. Both virus and aphid incidences could also be related to a range of crop and field characteristics, in particular sowing date, regions as defined by their geographical position, topography and climate, the proximity of the field to the sea, the extent of arable land in the vicinity of the field, and the aspect and size of the field. Proximity of cropped fields to setaside areas had no significant effect on either aphid or virus incidence. Copyright © 2004 Society of Chemical Industry
Molluscicidal effects of neem (Azadirachta indica) extracts on edible tropical land snails
Authors: Ebenso Ime E 
Published: January 2004

AbstractThe effects of 350, 500 and 700 mg kg−1 of crude extracts of neem, Azadirachta indica A Juss, on edible tropical land snails Archachatina marginata and Limicolaria aurora (Jay) were determined and compared with control using pawpaw, Carica papaya L as bait. Responses were measured through normal feeding, cessation of food intake, cessation of crawling, mucus secretion, lack of response to mechanical stimuli (mortality) and decomposition. Results showed no effects on the controls or snails exposed to neem seed oil extract. Crude extracts of bark, root and leaf of neem at 500 and 700 mg kg−1 produced mortality after exposure for 48 h for L aurora and 72 h for A marginata. Copyright © 2004 Society of Chemical Industry
Benzoylphenylurea residues in peppers and zucchinis grown in greenhouses: determination of decline times and pre‐harvest intervals by modelling
Authors: López‐López Trinidad , Martínez‐Vidal José L , Gil‐García María D , Martínez‐Galera María , Rodríguez‐Lallena José A 
Published: January 2004

AbstractResidue levels and degradation rates of five benzoylphenylurea insecticides were studied in zucchinis and peppers grown in experimental greenhouses in Almería (Spain). Benzoylphenylurea residues were analyzed by HPLC using on‐line post‐elution photoirradiation with fluorescence detection. Mathematically defined decline curves were established by determining optimal relationships between benzoylphenylurea residues and time, using different models. The models that best fitted the experimental data were those of first‐order for diflubenzuron, triflumuron, hexaflumuron and flufenoxuron in zucchini and RF first‐order models for the five insecticides in peppers and for lufenuron in zucchini. Half‐life times for the residues on the two vegetables were estimated from the optimal models. In order to guarantee safe consumption of the two vegetables, we have estimated suitable pre‐harvest intervals complying with the maximum residue levels established by the Spanish Government. In all cases, such pre‐harvest intervals were shorter than those specified by the manufacturers of commercial formulates. Experimental data for the five insecticides in peppers and for lufenuron in zucchini were also fitted to a first‐order model. Even though this function was legitimized statistically, estimations of decline times (T/2) and pre‐harvest intervals were quite different from those provided by the optimal model. Copyright © 2004 Society of Chemical Industry