Institute of Biotechnology AS CR, v.v.i., Laboratory of Structural Biology, Videnska 1083, 14200 Praha 4, Czech Republic.
Curr Med Chem. 2012;19(9):1300-9. doi: 10.2174/092986712799462667.
Recent years witnessed rapid expansion of our knowledge about structural features of human glutamate carboxypeptidase II (GCPII). There are over thirty X-ray structures of human GCPII (and of its close ortholog GCPIII) publicly available at present. They include structures of ligand-free wild-type enzymes, complexes of wild-type GCPII/GCPIII with structurally diversified inhibitors as well as complexes of the GCPII(E424A) inactive mutant with several substrates. Combined structural data were instrumental for elucidating the catalytic mechanism of the enzyme. Furthermore the detailed knowledge of the GCPII architecture and protein-inhibitor interactions offers mechanistic insight into structure-activity relationship studies and can be exploited for the rational design of novel GCPII-specific compounds. This review presents a summary of structural information that has been gleaned since 2005, when the first GCPII structures were solved.
近年来，我们对人类谷氨酸羧肽酶 II（GCPII）的结构特征的了解迅速扩展。目前，已有超过三十个人类 GCPII（及其密切的同源物 GCPIII）的 X 射线结构可供公开使用。这些结构包括无配体的野生型酶的结构、野生型 GCPII/GCPIII 与结构多样化的抑制剂的复合物以及 GCPII(E424A)失活突变体与几种底物的复合物。综合结构数据对于阐明酶的催化机制至关重要。此外，对 GCPII 结构和蛋白-抑制剂相互作用的详细了解为结构-活性关系研究提供了机制上的见解，并可用于新型 GCPII 特异性化合物的合理设计。本篇综述介绍了自 2005 年首次解决 GCPII 结构以来获得的结构信息的摘要。
