title: Coupling between catalytic site and collective dynamics: a requirement for mechanochemical activity of enzymes.
abstract: Growing evidence supports the view that enzymatic activity results from a subtle interplay between chemical kinetics and molecular motions. A systematic analysis is performed here to delineate the type and level of coupling between catalysis and conformational mechanics. The dynamics of a set of 98 enzymes representative of different EC classes are analyzed with the Gaussian network model (GNM) and compared with experimental data. In more than 70% of the examined enzymes, the global hinge centers predicted by the GNM are found to be colocalized with the catalytic sites experimentally identified. Low translational mobility (< 7%) is observed for the catalytic residues, consistent with the fine-tuned design of enzymes to achieve precise mechanochemical activities. Ligand binding sites, while closely neighboring catalytic sites, enjoy a moderate flexibility to accommodate the ligand binding. These findings could serve as additional criteria for assessing drug binding residues and could lessen the computational burden of substrate docking searches.
authors.affiliation: Department of Computational Biology, school of Medicine, University of Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Lee-Wei
authors.initials: LW
authors.lastname: Yang
authors.forename: Ivet
authors.initials: I
authors.lastname: Bahar
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D019295:Computational Biology; D003198:Computer Simulation; D004795:Enzyme Stability; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D009038:Motion; D011485:Protein Binding; D011487:Protein Conformation; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D004798:Enzymes; D008024:Ligands