Coupling between catalytic site and collective dynamics: a requirement for mechanochemical activity of enzymes.
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.
Yang
Lee-Wei
LW
Department of Computational Biology, school of Medicine, University of Pittsburgh, Pennsylvania 15261, USA.
Bahar
Ivet
I
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
D004798:Enzymes; D008024:Ligands