期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 18, 期 10, 页码 1102-U113出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2120
关键词
-
资金
- Ministry of Innovation, Science, Research and Technology of the German state of North Rhine-Westphalia
- Ruhr-University Bochum
- Germany's Excellence Initiative [DFG GSC 98/1]
- Robert A. Welch Foundation
- US National Institutes of Health [CA098799]
- Israel Science Foundation
- Kimmelman Center at the Weizmann Institute
- Ambach family fund
- VW Stiftung
Solvent dynamics can play a major role in enzyme activity, but obtaining an accurate, quantitative picture of solvent activity during catalysis is quite challenging. Here, we combine terahertz spectroscopy and X-ray absorption analyses to measure changes in the coupled water-protein motions during peptide hydrolysis by a zinc-dependent human metalloprotease. These changes were tightly correlated with rearrangements at the active site during the formation of productive enzyme-substrate intermediates and were different from those in an enzyme-inhibitor complex. Molecular dynamics simulations showed a steep gradient of fast-to-slow coupled protein-water motions around the protein, active site and substrate. Our results show that water retardation occurs before formation of the functional Michaelis complex. We propose that the observed gradient of coupled protein-water motions may assist enzyme-substrate interactions through water-polarizing mechanisms that are remotely mediated by the catalytic metal ion and the enzyme active site.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据