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Role of Water in the Enzymatic Catalysis: Study of ATP plus AMP -> 2ADP Conversion by Adenylate Kinase

Adkar, Bharat V and Jana, Biman and Bagchi, Biman (2011) Role of Water in the Enzymatic Catalysis: Study of ATP plus AMP -> 2ADP Conversion by Adenylate Kinase. In: Journal of Physical Chemistry A, The, 115 (16). pp. 3691-3697.

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Official URL: http://pubs.acs.org/doi/abs/10.1021/jp104787s

Abstract

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 stale 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.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Journal of Physical Chemistry A, The.
Department/Centre: Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited: 20 May 2011 06:41
Last Modified: 20 May 2011 06:41
URI: http://eprints.iisc.ernet.in/id/eprint/37678

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