Role of Repeated Conformational Transitions in Substrate Binding of Adenylate Kinase.

ABSTRACT: The catalytic cycle of the enzyme adenylate kinase involves large conformational motions between open and closed states. A previous single-molecule experiment showed that substrate binding tends to accelerate both the opening and the closing rates and that a single turnover event often involves multiple rounds of conformational switching. In this work, we showed that the repeated conformational transitions of adenylate kinase are essential for the relaxation of incorrectly bound substrates into the catalytically competent conformation by combining all-atom and coarse-grained molecular simulations. In addition, free energy calculations based on all-atom and coarse-grained models demonstrated that the enzyme with incorrectly bound substrates has much a lower free energy barrier for domain op

SUBMITTER: Lu J 

PROVIDER: S-EPMC9589722 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature