Protein flexibility and enzymatic catalysis.

The dynamic nature of protein structures has been recognized, established, and accepted as an intrinsic fundamental property with major consequences to their function. Nowadays, proteins are considered as networks of continuous motions, which reflect local flexibility and a propensity for global structural plasticity. Protein-protein and protein-small ligand interactions, signal transduction and assembly of macromolecular machines, allosteric regulation and thermal enzymatic adaptation are processes which require structural flexibility. In general, enzymes represent an attractive class among proteins in the study of protein flexibility and they can be used as model systems for understanding the implications of protein fluctuations to biological function. Flexibility of the active site is considered as a requirement for reduction of free energy barrier and acceleration of the enzymatic reaction while there is growing evidence which concerns the connection between flexibility and substrate turnover rate. Moreover, the role of conformational flexibility has been well established in connection with the accessibility of the active site, the binding of substrates and ligands, and release of products, stabilization and trapping of intermediates, orientation of the substrate into the binding cleft, adjustment of the reaction environment, etc.