Calixto Ana Rita, Moreira Cátia, Kamerlin Shina Caroline Lynn
Department of Chemistry - BMC, Uppsala University, BMC Box 576, S-751 23 Uppsala, Sweden.
ACS Omega. 2020 Feb 28;5(9):4380-4385. doi: 10.1021/acsomega.0c00240. eCollection 2020 Mar 10.
GTP hydrolysis is central to biology, being involved in regulating a wide range of cellular processes. However, the mechanisms by which GTPases hydrolyze this critical reaction remain controversial, with multiple mechanistic possibilities having been proposed based on analysis of experimental and computational data. In this mini-review, we discuss advances in our understanding of biological GTP hydrolysis based on recent computational studies and argue in favor of solvent-assisted hydrolysis as a conserved mechanism among GTPases. A concrete understanding of the fundamental mechanisms by which these enzymes facilitate GTP hydrolysis will have significant impact both for drug discovery efforts and for unraveling the role of oncogenic mutations.
GTP水解对生物学至关重要，参与调控广泛的细胞过程。然而，GTP酶水解这一关键反应的机制仍存在争议，基于对实验和计算数据的分析，已提出多种可能的机制。在本综述中，我们基于最近的计算研究讨论了我们对生物GTP水解理解的进展，并支持溶剂辅助水解作为GTP酶中的一种保守机制。具体了解这些酶促进GTP水解的基本机制，将对药物研发工作以及阐明致癌突变的作用产生重大影响。
