bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal demonstration of afferent vessels and progressive thrombosis in a torcular malformation
Authors: Grangé G. , LeTohic A. , Merzoug V. , Adamsbaum C. 
Published: May 2007

AbstractObjectivesTo elucidate a part of the prenatal natural history of dural sinus malformation of the posterior fossa.MethodsUltrasound and magnetic resonance imaging were performed from 31 to 32 weeks' gestation.ResultsWe observed the progressive development of a thrombus that was visible as an expanding hyperechoic round area within a cystic mass of the posterior fossa. It was characterized, as expected for a vascular malformation, by the presence of blood flow into the aneurismal cavity. Color doppler identified superior sagittal and straight sinuses, and distinguished that their flow continued into the dilated torcular. Prenatal magnetic resonance imaging confirmed an arteriovenous malformation involving the dural sinus.ConclusionThe vascular malformation had a fixed volume and preceded the thrombosis, which formed within several days. The present case is the first report with all the prenatal sonographic features of this condition. Copyright © 2007 John Wiley & Sons, Ltd.
Array‐CGH analysis of cell‐free fetal DNA in 10 mL of amniotic fluid supernatant
Authors: Lapaire Olav , Lu Xin‐Yan , Johnson Kirby L. , Jarrah Zina , Stroh Helene , Cowan Janet M. , Tantravahi Umadevi , Bianchi Diana W. 
Published: May 2007

AbstractBackgroundPreviously, we showed that analysis of amniotic fluid (AF) supernatant cell‐free fetal (cff) DNA using DNA microarrays (array‐CGH) allows for detection of whole chromosome differences between test and reference DNA. Subsequent technical advances have increased both the yield and quality of extracted cffDNA. Here we determined whether array‐CGH using smaller volumes of both fresh and frozen AF cffDNA could identify fetal aneuploidy.MethodsCffDNA was extracted from 10 mL of residual AF supernatant. The test AF samples (n = 10) included one with a normal karyotype, and nine with the following fetal aneuploidies: trisomies 13 (n = 1), 18 (n = 3), 21 (n = 2), trisomy 9 mosaicism (47,XX,+ 9[18]/46,XX[2]), triploidy (69,XXY) and Turner syndrome (45,X).ResultsArray‐CGH using AF cffDNA from aneuploid fetuses, compared to euploid reference AF cffDNA, detected whole chromosome aneuploidy in 8 of 9 cases tested, including the case of trisomy 9 mosaicism. The case of triploidy was not detected.ConclusionsCffDNA extracted from 10 mL AF supernatant can be analyzed using array‐CGH to correctly identify human chromosome abnormalities. This technology allows for rapid screening of AF samples for whole chromosomal changes by using routinely discarded supernatant, and may augment standard prenatal karyotyping techniques by providing additional molecular information. Copyright © 2007 John Wiley & Sons, Ltd.
Parallel tempering molecular dynamics folding simulation of a signal peptide in explicit water
Authors: Höfinger Siegfried , Almeida Benjamin , Hansmann Ulrich H. E. 
Published: May 2007

AbstractParallel temperature molecular dynamics simulations are used to explore the folding of a signal peptide, a short but functionally independent domain at the N‐terminus of proteins. The peptide has been analyzed previously by NMR, and thus a solid reference state is provided with the experimental structure. Particular attention is paid to the role of water considered in full atomic detail. Different partial aspects in the folding process are quantified. The major group of obtained structures matches the NMR structure very closely. An important biological consequence is that in vivo folding of signal peptides seems to be possible within aqueous environments. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Structure‐based virtual ligand screening with LigandFit: Pose prediction and enrichment of compound collections
Authors: Montes Matthieu , Miteva Maria A. , Villoutreix Bruno O. 
Published: May 2007

AbstractVirtual ligand screening methods based on the structure of the receptor are extensively used to facilitate the discovery of lead compounds. In the present study, we investigated the LigandFit package on four different proteins (coagulation factor VIIa, estrogen receptor, thymidine kinase, and neuraminidase), a relatively large compound collection of 65,560 unique “drug‐like” molecules and four focused libraries (1950 molecules each). We performed virtual screening experiments with the large database and evaluated six scoring functions available in the package (DockScore, LigScore1, LigScore2, PLP1, PLP2, and PMF). The results showed that LigandFit is an efficient program, especially when used with LigScore1. Similar computations were carried out using focused libraries. In this situation the LigScore1 scoring function outperformed the other ones on three out of the four proteins tested. Even for the difficult neuraminidase case, the LigandFit/LigScore1 combination was still reasonably successful. Assessment of docking accuracy was also performed and again, we found that LigandFit (with DockScore and the CFF parameters) was performing well. On the basis of these results and observed increased enrichments after LigandFit/Ligscore1 screening on focused libraries, we suggest that using this program as a final step of a hierarchical protocol can be very beneficial to assist lead finding. Proteins 2007. © 2007 Wiley‐Liss, Inc.
The crystal structure of the secreted aspartic proteinase 3 from Candida albicans and its complex with pepstatin A
Authors: Borelli Claudia , Ruge Elisabeth , Schaller Martin , Monod Michel , Korting Hans Christian , Huber Robert , Maskos Klaus 
Published: May 2007

AbstractThe family of secreted aspartic proteinases (Sap) encoded by 10 SAP genes is an important virulence factor during Candida albicans (C. albicans) infections. Antagonists to Saps could be envisioned to help prevent or treat candidosis in immunocompromised patients. The knowledge of several Sap structures is crucial for inhibitor design; only the structure of Sap2 is known. We report the 1.9 and 2.2 Å resolution X‐ray crystal structures of Sap3 in a stable complex with pepstatin A and in the absence of an inhibitor, shedding further light on the enzyme inhibitor binding. Inhibitor binding causes active site closure by the movement of a flap segment. Comparison of the structures of Sap3 and Sap2 identifies elements responsible for the specificity of each isoenzyme. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Using molecular dynamics to map interaction networks in an aminoacyl‐tRNA synthetase
Authors: Budiman Michael E. , Knaggs Michael H. , Fetrow Jacquelyn S. , Alexander Rebecca W. 
Published: May 2007

AbstractLong‐range functional communication is a hallmark of many enzymes that display allostery, or action‐at‐a‐distance. Many aminoacyl‐tRNA synthetases can be considered allosteric, in that their trinucleotide anticodons bind the enzyme at a site removed from their catalytic domains. Such is the case with E. coli methionyl‐tRNA synthase (MetRS), which recognizes its cognate anticodon using a conserved tryptophan residue 50 Å away from the site of tRNA aminoacylation. The lack of details regarding how MetRS and tRNAMet interact has limited efforts to deconvolute the long‐range communication that occurs in this system. We have used molecular dynamics simulations to evaluate the mobility of wild‐type MetRS and a Trp‐461 variant shown previously by experiment to be deficient in tRNA aminoacylation. The simulations reveal that MetRS has significant mobility, particularly at structural motifs known to be involved in catalysis. Correlated motions are observed between residues in distant structural motifs, including the active site, zinc binding motif, and anticodon binding domain. Both mobility and correlated motions decrease significantly but not uniformly upon substitution at Trp‐461. Mobility of some residues is essentially abolished upon removal of Trp‐461, despite being tens of Ångstroms away from the site of mutation and solvent exposed. This conserved residue does not simply participate in anticodon binding, as demonstrated experimentally, but appears to mediate the protein's distribution of structural ensembles. Finally, simulations of MetRS indicate that the ligand‐free protein samples conformations similar to those observed in crystal structures with substrates and substrate analogs bound. Thus, there are low energetic barriers for MetRS to achieve the substrate‐bound conformations previously determined by structural methods. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Generation of blood group specificity: New insights from structural studies on the complexes of A‐ and B‐reactive saccharides with basic winged bean agglutinin
Authors: Kulkarni Kiran A. , Katiyar Samiksha , Surolia Avadhesha , Vijayan Mamannamana , Suguna Kaza 
Published: May 2007

AbstractBasic winged bean agglutinin binds A‐blood group substance with higher affinity and B‐blood group substance with lesser affinity. It does not bind the O substance. The crystal structures of the lectin, complexed with A‐reactive and B‐reactive di and tri saccharides, have been determined. In addition, the complexes of the lectin with fucosylated A‐trisaccharides and B‐trisaccharides and with a variant of the A‐trisaccharide have been modeled. These structures and models provide valuable insights into the structural basis of blood group specificities. All the four carbohydrate binding loops of the lectin contribute to the primary combining site while the loop of variable length contributes to the secondary binding site. In a significant advance to the current understanding, the interactions at the secondary binding site also contribute substantially, albeit in a subtle manner, to determine the blood group specificity. Compared with the interactions of the B‐trisaccharide with the lectin, the third sugar residue of the A‐reactive trisacharide forms an additional hydrogen bond with a lysine residue in the variable loop. In the former, the formation of such a hydrogen bond is prevented by a shift in the orientation of third sugar resulting from an internal hydrogen bond in it. The formation of this bond is also facilitated by an interaction dependent change in the rotamer conformation of the lysyl residue of the variable loop. Thus, the difference in the interactions at the secondary site is generated by coordinated movements in the ligand as well as the protein. A comparison of the crystal structure and the model of the complex involving the variant of the A‐trisaccharide results in the delineation of the relative contributions of the interactions at the primary and the secondary sites in determining blood group specificity. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Modeling and analysis of molecularinteraction between Smurf1‐WW2 domain and various isoforms of LIM mineralization protein
Authors: Sangadala Sreedhara , Boden Scott D. , Metpally Raghu Prasad Rao , Reddy Boojala Vijay B. 
Published: May 2007

AbstractLIM Mineralization Protein‐1 (LMP‐1) has been cloned and shown to be osteoinductive. Our efforts to understand the mode of action of LMP‐1 led to the determination that LMP‐1 interacts with Smad Ubiquitin Regulatory Factor‐1 (Smurf1). Smurf1 targets osteogenic Smads, Smad1/5, for ubiquitin‐mediated proteasomal degradation. Smurf1 interaction with LMP‐1 or Smads is based on the presence of unique WW‐domain interacting motif in these target molecules. By performing site‐directed mutagenesis and binding studies in vitro on purified recombinant proteins, we identified a specific motif within the osteogenic region of several LMP isoforms that is necessary for Smurf1 interaction. Similarly, we have identified that the WW2 domain of Smurf1 is necessary for target protein interaction. Here, we present a homology‐based modeling of the Smurf1 WW2 domain and its interacting motif of LMP‐1. We performed computational docking of the interacting domains in Smurf1 and LMPs to identify the key amino acid residues involved in their binding regions. In support of the computational predictions, we also present biochemical evidence supporting the hypothesis that the physical interaction of Smurf1 and osteoinductive forms of LMP may prevent Smurf1 from targeting osteogenic Smads by ubiquitin‐mediated proteasomal degradation. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Constructing ensembles of flexible fragments in native proteins by iterative stochastic elimination is relevant to protein–protein interfaces
Authors: Noy Efrat , Tabakman Tal , Goldblum Amiram 
Published: May 2007

AbstractWe investigate the extent to which ensembles of flexible fragments (FF), generated by our loop conformational search method, include conformations that are near experimental and reflect conformational changes that these FFs undergo when binary protein–protein complexes are formed. Twenty‐eight FFs, which are located in protein–protein interfaces and have different conformations in the bound structure (BS) and unbound structure (UbS) were extracted. The conformational space of these fragments in the BS and UbS was explored with our method which is based on the iterative stochastic elimination (ISE) algorithm. Conformational search of BSs generated bound ensembles and conformational search of UbSs produced unbound ensembles. ISE samples conformations near experimental (less than 1.05 Å root mean square deviation, RMSD) for 51 out of the 56 examined fragments in the bound and unbound ensembles. In 14 out of the 28 unbound fragments, it also samples conformations within 1.05 Å from the BS in the unbound ensemble. Sampling the bound conformation in the unbound ensemble demonstrates the potential biological relevance of the predicted ensemble. The 10 lowest energy conformations are the best choice for docking experiments, compared with any other 10 conformations of the ensembles. We conclude that generating conformational ensembles for FFs with ISE is relevant to FF conformations in the UbS and BS. Forming ensembles of the isolated proteins with our method prior to docking represents more comprehensively their inherent flexibility and is expected to improve docking experiments compared with results obtained by docking only UbSs. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Structural and biochemical characterization of inhibitor‐1α
Authors: Huang Hsien‐Bin , Chen Yi‐Chen , Lee Ting‐Ting , Huang Yi‐Choang , Liu Hsin‐Tzu , Liu Chen‐Kuang , Tsay Huey‐Jen , Lin Ta‐Hsien 
Published: May 2007

AbstractInhibitor‐1α is one of the isoforms of human protein phosphatase inhibitor‐1. It is a product of alternative splicing of inhibitor‐1 gene and lacks 51 internal amino acids from residue 84 to 134 of inhibitor‐1. Here we have characterized the structural and biochemical properties of inhibitor‐1α. Structural analysis of recombinant inhibitor‐1α by NMR spectroscopy revealed that inhibitor‐1α adopts a predominantly random coil conformation. Excluding the region from residue 84 to 134 of inhibitor‐1, the structural features of inhibitor‐1 and inhibitor‐1α are almost the same as each other. The IC50 value of inhibitor‐1α in inhibition of Protein phosphatase‐1 (PP1) is comparable to that of inhibitor‐1, indicating that inhibitor‐1α is a potent inhibitor of PP1 when Thr‐35 is phosphorylated by PKA. For phosphorylation by PKA and dephosphorylation by protein phosphatase‐1, ‐2A, and ‐2B, the measured kinetic parameters of inhibitor‐1α are very close to those of inhibitor‐1. Taken together, these results suggest that inhibitor‐1α preserves the structure of inhibitor‐1, the PP1 inhibitory activity and the functional specificities toward phosphorylation by PKA and dephosphorylation by protein phosphatase‐1, ‐2A, and ‐2B. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Atomic contacts in protein structures. A detailed analysis of atomic radii, packing, and overlaps
Authors: Seeliger Daniel , de Groot Bert L. 
Published: May 2007

AbstractA rigorous quantitative assessment of atomic contacts and packing in native protein structures is presented. The analysis is based on optimized atomic radii derived from a set of high‐resolution protein structures and reveals that the distribution of atomic contacts and overlaps is a structural constraint in proteins, irrespective of structural or functional classification and size. Furthermore, a newly developed method for calculating packing properties is introduced and applied to sets of protein structures at different levels of resolution. The results show that limited resolution yields decreasing packing quality, which underscores the relevance of packing considerations for structure prediction, design, dynamics, and docking. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Studies of the molten globule state of ferredoxin: Structural characterization and implications on protein folding and iron–sulfur center assembly
Authors: Leal Sónia S. , Gomes Cláudio M. 
Published: May 2007

AbstractThe biological insertion of iron–sulfur clusters (Fe–S) involves the interaction of (metallo) chaperons with a partly folded target polypeptide. In this respect, the study of nonnative protein conformations in iron–sulfur proteins is relevant for the understanding of the folding process and cofactor assembly. We have investigated the formation of a molten globule state in the [3Fe4S][4Fe4S] ferredoxin from the thermophilic archaeon Acidianus ambivalens (AaFd), which also contains a structural zinc site. Biophysical studies have shown that, at acidic pH, AaFd retains structural folding and metal centers. However, upon increasing the temperature, a series of successive modifications occur within the protein structure: Fe–S disassembly, loss of tertiary contacts and dissociation of the Zn2+ site, which is simultaneous to alterations on the secondary structure. Upon cooling, an apo‐ferredoxin state is obtained, with characteristics of a molten globule: compactness identical to the native form; similar secondary structure evidenced by far‐UV CD; no near‐UV CD detected tertiary contacts; and an exposure of the hydrophobic surface evidenced by 1‐anilino naphthalene‐8‐sulfonic acid (ANS) binding. In contrast to the native form, this apo ferredoxin state undergoes reversible thermal and chemical unfolding. Its conformational stability was investigated by guanidinium chloride denaturation and this state is ∼1.5 kcal mol−1 destabilised in respect to the holo ferredoxin. The single tryptophan located nearby the Fe–S pocket probed the conformational dynamics of the molten globule state: fluorescence quenching, red edge emission shift analysis and resonance energy transfer to bound ANS evidenced a restricted mobility and confinement within a hydrophobic environment. The possible physiological relevance of molten globule states in Fe–S proteins and the hypothesis that their structural flexibility may be important to the understanding of metal center insertion are discussed. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Conformational contagion in a protein: Structural properties of a chameleon sequence
Authors: Takano Kazufumi , Katagiri Yoshiaki , Mukaiyama Atsushi , Chon Hyongi , Matsumura Hiroyoshi , Koga Yuichi , Kanaya Shigenori 
Published: May 2007

AbstractCertain sequences, known as chameleon sequences, take both α‐ and β‐conformations in natural proteins. We demonstrate that a wild chameleon sequence fused to the C‐terminal α‐helix or β‐sheet in foreign stable proteins from hyperthermophiles forms the same conformation as the host secondary structure. However, no secondary structural formation is observed when the sequence is attached to the outside of the secondary structure. These results indicate that this sequence inherently possesses an ability to make either α‐ or β‐conformation, depending on the sequentially neighboring secondary structure if little other nonlocal interaction occurs. Thus, chameleon sequences take on a satellite state through contagion by the power of a secondary structure. We propose this “conformational contagion” as a new nonlocal determinant factor in protein structure and misfolding related to protein conformational diseases. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Fold recognition by concurrent use of solvent accessibility and residue depth
Authors: Liu Song , Zhang Chi , Liang Shide , Zhou Yaoqi 
Published: May 2007

AbstractRecognizing the structural similarity without significant sequence identity (called fold recognition) is the key for bridging the gap between the number of known protein sequences and the number of structures solved. Previously, we developed a fold‐recognition method called SP3 which combines sequence‐derived sequence profiles, secondary‐structure profiles and residue‐depth dependent, structure‐derived sequence profiles. The use of residue‐depth‐dependent profiles makes SP3 one of the best automatic predictors in CASP 6. Because residue depth (RD) and solvent accessible surface area (solvent accessibility) are complementary in describing the exposure of a residue to solvent, we test whether or not incorporation of solvent‐accessibility profiles into SP3 could further increase the accuracy of fold recognition. The resulting method, called SP4, was tested in SALIGN benchmark for alignment accuracy and Lindahl, LiveBench 8 and CASP7 blind prediction for fold recognition sensitivity and model‐structure accuracy. For remote homologs, SP4 is found to consistently improve over SP3 in the accuracy of sequence alignment and predicted structural models as well as in the sensitivity of fold recognition. Our result suggests that RD and solvent accessibility can be used concurrently for improving the accuracy and sensitivity of fold recognition. The SP4 server and its local usage package are available on http://sparks.informatics.iupui.edu/SP4. Proteins 2007. © 2007 Wiley‐Liss, Inc.
A model‐based proposal for the role of UreF as a GTPase‐activating protein in the urease active site biosynthesis
Authors: Salomone‐Stagni Marco , Zambelli Barbara , Musiani Francesco , Ciurli Stefano 
Published: May 2007

AbstractUreF is a protein that plays a role in the in vivo urease activation as a chaperone involved in the insertion of two Ni2+ ions in the apo‐urease active site. The molecular details of this process are unknown. In the absence of any molecular information on the UreF protein class, and as a step toward the comprehension of the relationships between UreF function and structure, we applied a structural modeling approach to infer useful biochemical knowledge on Bacillus pasteurii UreF (BpUreF). Similarity searches and multiple alignment of UreF protein sequences indicated that this class of proteins has a low homology with proteins of known structure. Fold recognition methods were therefore used to identify useful protein structural templates to model the structure of BpUreF. In particular, the templates belong to the class of GTPase‐activating proteins. Modeling of BpUreF based on these templates was performed using the program MODELLER. The structure validation yielded good statistics, indicating that the model is plausible. This result suggests a role for UreF in urease active site biosynthesis as a regulator of the activity of UreG, a small G protein involved in the in vivo apo‐urease activation process and established to catalyze GTP hydrolysis. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Intrinsic disorder in yeast transcriptional regulatory network
Authors: Singh Gajinder Pal , Dash Debasis 
Published: May 2007

AbstractIntrinsic disorder has been shown to be important in mediating protein–protein and protein–DNA interactions. Proteins involved in regulatory functions are particularly enriched in intrinsic disorder. In this study we explored the role of intrinsic disorder in transcriptional regulatory network of yeast. Using disorder prediction programs we show that transcription factors (TFs) regulating large number of targets (transcriptional hubs) have significantly increased intrinsic disorder, though targets regulated by multiple TFs did not show increased intrinsic disorder. Intrinsic disorder may allow these transcriptional hubs to bind to diverse promoter regions of their targets in different contexts, and may also allow complex regulatory control of transcriptional hubs that are involved in coordinating different cellular processes. Proteins 2007. © 2007 Wiley‐Liss, Inc.