Department of Biology, University of Crete, Heraklion, Crete, Greece.
Adv Protein Chem Struct Biol. 2012;87:181-218. doi: 10.1016/B978-0-12-398312-1.00007-X.
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.
蛋白质结构的动态性质已被认识、确立并被接受为一种固有基本特性，对其功能有重大影响。如今，蛋白质被视为连续运动的网络，反映了局部的灵活性和整体结构可塑性。蛋白质-蛋白质和蛋白质-小分子配体相互作用、信号转导和大分子机器的组装、变构调节和热酶适应都是需要结构灵活性的过程。一般来说，酶在研究蛋白质灵活性方面是蛋白质中一个有吸引力的类别，它们可以用作模型系统，以了解蛋白质波动对生物功能的影响。活性位点的灵活性被认为是降低自由能势垒和加速酶反应的要求，而越来越多的证据表明灵活性与底物周转率之间存在联系。此外，构象灵活性在活性位点的可及性、底物和配体的结合以及产物的释放、中间产物的稳定和捕获、底物进入结合裂隙的取向、反应环境的调整等方面的作用已得到充分证实。
