Journal Issue - Volume 15 Issue 9 (September 2006)
Configurational‐bias sampling technique for predicting side‐chain conformations in proteins
- Tushar Jain, David S. Cerutti, J. Andrew McCammon
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062165906 (p 2029-2039)
Abstract Prediction of side‐chain conformations is an important component of several biological modeling applications. In this work, we have developed and tested an advanced Monte Carlo sampling strategy for predicting side‐chain conformations. Our method is based on a cooperative rearrangement of atoms that belong to a group of neighboring side‐chains. This rearrangement is accomplished by deleting groups of atoms from the...
The refolding of different α‐fetoprotein variants
- Susanna S.J. Leong, Anton P.J. Middelberg
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062262406 (p 2040-2050)
Abstract The effect of glycosylation on AFP foldability was investigated by parallel quantitative and qualitative analyses of the refolding of glycosylated and nonglycosylated AFP variants. Both variants were successfully refolded by dialysis from the denatured‐reduced state, attaining comparable “refolded peak” profiles and refolding yields as determined by reversed‐phase HPLC analysis. Both refolded variants also showed comparable...
A model for the coupling of α‐helix and tertiary contact formation
- Andrew C. Hausrath
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062292106 (p 2051-2061)
Abstract Peptides corresponding to excised α‐helical segments of natural proteins can spontaneously form helices in solution. However, peptide helices are usually substantially less stable in solution than in the structural context of a folded protein, because of the additional interactions possible between helices in a protein. Such interactions can be thought of as coupling helix formation and tertiary contact formation. The...
Fundamental processes of protein folding: Measuring the energetic balance between helix formation and hydrophobic interactions
- Wujing Xian, Peter J. Connolly, Marcela Oslin, Andrew C. Hausrath, John J. Osterhout
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062297006 (p 2062-2070)
Abstract Theories of protein folding often consider contributions from three fundamental elements: loops, hydrophobic interactions, and secondary structures. The pathway of protein folding, the rate of folding, and the final folded structure should be predictable if the energetic contributions to folding of these fundamental factors were properly understood. αtα is a helix‐turn‐helix peptide that was developed by de novo design to...
Peptide deformylase is a potential target for anti‐ Helicobacter pylori drugs: Reverse docking, enzymatic assay, and X‐ray crystallography validation
- Jianhua Cai, Cong Han, Tiancen Hu, Jian Zhang, Dalei Wu, Fangdao Wang, Yunqing Liu, Jianping Ding, Kaixian Chen, Jianmin Yue, Xu Shen, Hualiang Jiang
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062238406 (p 2071-2081)
Abstract Colonization of human stomach by the bacterium Helicobacter pylori is a major causative factor for gastrointestinal illnesses and gastric cancer. However, the discovery of anti‐H. pylori agents is a difficult task due to lack of mature protein targets. Therefore, identifying new molecular targets for developing new drugs against H. pylori is obviously necessary. In this study, the in‐house potential drug target database (PDTD, ...
Revisiting the Voronoi description of protein–protein interfaces
- Frédéric Cazals, Flavien Proust, Ranjit P. Bahadur, Joël Janin
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062245906 (p 2082-2092)
Abstract We developed a model of macromolecular interfaces based on the Voronoi diagram and the related alpha‐complex, and we tested its properties on a set of 96 protein–protein complexes taken from the Protein Data Bank. The Voronoi model provides a natural definition of the interfaces, and it yields values of the number of interface atoms and of the interface area that have excellent correlation coefficients with those of the...
The structure of GDP‐4‐keto‐6‐deoxy‐
6 ‐dependent enzyme - Paul D. Cook, James B. Thoden, Hazel M. Holden
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062328306 (p 2093-2106)
Abstract l‐Colitose is a 3,6‐dideoxysugar found in the O‐antigens of some Gram‐negative bacteria such as Escherichia coli and in marine bacteria such as Pseudoalteromonas tetraodonis. The focus of this investigation, GDP‐4‐keto‐6‐deoxy‐d‐mannose‐3‐dehydratase, catalyzes the third step in colitose production, which is the removal of the hydroxyl group at C3′ of GDP‐4‐keto‐6‐deoxymannose. It is an especially intriguing PLP‐dependent enzyme in that it acts as...
Identification of an alcohol binding site in the first cysteine‐rich domain of protein kinase C δ
- Joydip Das, Xiaojuan Zhou, Keith W. Miller
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062237606 (p 2107-2119)
Abstract Protein kinase C (PKC) is an important signal transduction protein whose cysteine‐rich regulatory domain C1 has been proposed to interact with general anesthetics in both of its diacylglycerol/phorbol ester–binding subdomains, the tandem repeats C1A and C1B. Previously, we identified an allosteric binding site on one of the two cysteine‐rich domains, PKCδ C1B. To test the hypothesis that there is an additional anesthetic...
Residue centrality, functionally important residues, and active site shape: Analysis of enzyme and non‐enzyme families
- Antonio del Sol, Hirotomo Fujihashi, Dolors Amoros, Ruth Nussinov
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062249106 (p 2120-2128)
Abstract The representation of protein structures as small‐world networks facilitates the search for topological determinants, which may relate to functionally important residues. Here, we aimed to investigate the performance of residue centrality, viewed as a family fold characteristic, in identifying functionally important residues in protein families. Our study is based on 46 families, including 29 enzyme and 17 non‐enzyme...
Two crystal structures of Trichoderma reesei hydrophobin HFBI—The structure of a protein amphiphile with and without detergent interaction
- Johanna Hakanpää, Géza R. Szilvay, Heidi Kaljunen, Mirko Maksimainen, Markus Linder, Juha Rouvinen
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062326706 (p 2129-2140)
Abstract Hydrophobins are small fungal proteins that are highly surface active and possess a unique ability to form amphiphilic membranes through spontaneous self‐assembly. The first crystal structure of a hydrophobin, Trichoderma reesei HFBII, revealed the structural basis for the function of this amphiphilic protein—a patch consisting of hydrophobic side chains on the protein surface. Here, the crystal structures of a native and a variant T....
Effects of mutation at the D‐J H junction on affinity, specificity, and idiotypy of anti‐progesterone antibody DB3
- Mingyue He, Maureen Hamon, Hong Liu, Adam L. Corper, Michael J. Taussig
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062236806 (p 2141-2148)
Abstract The crystal structures of the Fab′ fragment of the anti‐progesterone monoclonal antibody DB3 and its complexes with steroid haptens have shown that the D‐JH junctional residue TrpH100 is a key contributor to binding site interactions with ligands. The indole group of TrpH100 also undergoes a significant conformational change between the bound and unliganded states, effectively opening and closing the combining site...
Solution structure of GOPC PDZ domain and its interaction with the C‐terminal motif of neuroligin
- Xiang Li, Jiahai Zhang, Zanxia Cao, Jihui Wu, Yunyu Shi
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062087506 (p 2149-2158)
Abstract GOPC (Golgi‐associated PDZ and coiled‐coil motif‐containing protein) represents a PDZ domain‐containing protein associated with the Golgi apparatus, which plays important roles in vesicular trafficking in secretory and endocytic pathways. GOPC interacts with many other proteins, such as the Wnt receptors Frizzled 8 and neuroligin via its PDZ domain. Neuroligin is a neural cell‐adhesion molecule of the post‐synapse, which...
Engineered lanthanide‐binding metallohomeodomains: Designing folded chimeras by modular turn substitution
- Sunghyuk Lim, Sonya J. Franklin
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062365506 (p 2159-2165)
Abstract A series of chimeric metallohomeodomains are described, engineered by rational design of a flexible Ca/Ln binding site into a DNA‐binding scaffold. A modular turn‐substitution approach was used to create proteins that both bind DNA and lanthanide ions, while retaining the secondary structure of the full homeodomain (determined by circular dichroism [CD]). Four similar metallohomeodomains were designed (C1–C4), their...
The folding mechanism of collagen‐like model peptides explored through detailed molecular simulations
- Collin M. Stultz
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062124606 (p 2166-2177)
Abstract Collagen has a unique folding mechanism that begins with the formation of a triple‐helical structure near its C terminus followed by propagation of this structure to the N terminus. To elucidate factors that affect the folding of collagen, we explored the folding pathway of collagen‐like model peptides using detailed molecular simulations with explicit solvent. Using biased molecular dynamics we examined the latter stages...
Comparative analysis and “expression space” coverage of the production of prokaryotic membrane proteins for structural genomics
- Sachin Surade, Markus Klein, Peggy C. Stolt‐Bergner, Cornelia Muenke, Ankita Roy, Hartmut Michel
- Published in Wiley Interscience on Jan 01, 2009
- DOI: 10.1110/ps.062312706 (p 2178-2189)
Abstract Membrane proteins comprise up to one‐third of prokaryotic and eukaryotic genomes, but only a very small number of membrane protein structures are known. Membrane proteins are challenging targets for structural biology, primarily due to the difficulty in producing and purifying milligram quantities of these proteins. We are evaluating different methods to produce and purify large numbers of prokaryotic membrane proteins for...




