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Role of Water in the Enzymatic Catalysis: Study of ATP + AMP → 2ADP Conversion by Adenylate Kinase.
MedLine Citation:
PMID:  20836529     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The catalytic conversion ATP + AMP → 2ADP by the enzyme adenylate kinase (ADK) involves the binding of one ATP molecule to the LID domain and one AMP molecule to the NMP domain. The latter is followed by a phosphate transfer and then the release of two ADP molecules. We have computed a novel two-dimensional configurational free energy surface (2DCFES), with one reaction coordinate each for the LID and the NMP domain motions, while considering explicit water interactions. Our computed 2DCFES clearly reveals the existence of a stable half-open half-closed (HOHC) intermediate state of the enzyme. Cycling of the enzyme through the HOHC state reduces the conformational free energy barrier for the reaction by about 20 kJ/mol. We find that the stability of the HOHC state (missed in all earlier studies with implicit solvent model) is largely because of the increase of specific interactions of the polar amino acid side chains with water, particularly with the arginine and the histidine residues. Free energy surface of the LID domain is rather rugged, which can conveniently slow down LID's conformational motion, thus facilitating a new substrate capture after the product release in the catalytic cycle.
Authors:
Bharat V Adkar; Biman Jana; Biman Bagchi
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Publication Detail:
Type:  Journal Article     Date:  2010-09-13
Journal Detail:
Title:  The journal of physical chemistry. A     Volume:  115     ISSN:  1520-5215     ISO Abbreviation:  J Phys Chem A     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9890903     Medline TA:  J Phys Chem A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3691-7     Citation Subset:  IM    
Affiliation:
Solid State and Structural Chemistry Unit, Indian Institute of Science , Bangalore 560012, India.
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