Joseph D, Petsko G A, Karplus M
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
Science. 1990 Sep 21;249(4975):1425-8. doi: 10.1126/science.2402636.
Triosephosphate isomerase (TIM) is used as a model system for the study of how a localized conformational change in a protein structure is produced and related to enzyme reactivity. An 11-residue loop region moves more than 7 angstroms and closes over the active site when substrate binds. The loop acts like a "lid" in that it moves rigidly and is attached by two hinges to the remainder of the protein. The nature of the motion appears to be built into the loop by conserved residues; the hinge regions, in contrast, are not conserved. Results of molecular dynamics calculations confirm the structural analysis and suggest a possible ligand-induced mechanism for loop closure.
磷酸丙糖异构酶（TIM）被用作一个模型系统，用于研究蛋白质结构中局部构象变化是如何产生的以及与酶活性的关系。当底物结合时，一个由11个残基组成的环区域移动超过7埃并封闭活性位点。该环的作用类似于一个“盖子”，它刚性移动并通过两个铰链连接到蛋白质的其余部分。这种运动的性质似乎由保守残基构建到环中；相比之下，铰链区域并不保守。分子动力学计算结果证实了结构分析，并提出了一种可能的配体诱导的环封闭机制。
