Role of Repeated Conformational Transitions in Substrate Binding of Adenylate Kinase.
J Phys Chem B
; 126(41): 8188-8201, 2022 10 20.
Article
in En
| MEDLINE
| ID: mdl-36222098
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 opening compared to that with the correct substrate conformation, which may explain the the acceleration of the domain opening rate by substrate binding. The results of this work provide mechanistic understanding to previous experimental observations and shed light onto the interplay between conformational dynamics and enzyme catalysis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenylate Kinase
/
Molecular Dynamics Simulation
Language:
En
Journal:
J Phys Chem B
Journal subject:
QUIMICA
Year:
2022
Document type:
Article
Affiliation country:
China
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA