Abstract
The NADPH-dependent reduction of glucose reaction that is catalyzed by Aldose Reductase (AR) follows a sequential ordered kinetic mechanism in which the co-factor NADPH binds to the enzyme prior to the aldehyde substrate. The kinetic/structural experiments have found a conformational change involving a hinge-like movement of a surface loop (residues 213-224) which is anticipated to take place upon the binding of the diphosphate moiety of NADPH. The reorientation of this loop, expected to permit the release of NADP+, represents the rate-limiting step of the catalytic mechanism. This study reveals: 1) The Translation/Libration/Screw (TLS) analysis of absolute B-factors of apo AR crystal structures indicates that the 212-224 loop might move as a rigid group. 2) Residues that make the flexible loop slide in the AR binary and ternary complexes. 3) The normalized B-factors separate this segment into three differnt clusters with fewer residues.
Keywords: Aldo-keto reductase, B-factor, clustering, crystal structure, statistical analysis, structural dynamics, TLS.
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Current Proteomics
Title:B-factor Analysis and Conformational Rearrangement of Aldose Reductase
Volume: 11 Issue: 3
Author(s): Ganesaratnam K. Balendiran, J. Rajendran Pandian, Evin Drake, Anubhav Vinayak, Malkhey Verma and Duilio Cascio
Affiliation:
Keywords: Aldo-keto reductase, B-factor, clustering, crystal structure, statistical analysis, structural dynamics, TLS.
Abstract: The NADPH-dependent reduction of glucose reaction that is catalyzed by Aldose Reductase (AR) follows a sequential ordered kinetic mechanism in which the co-factor NADPH binds to the enzyme prior to the aldehyde substrate. The kinetic/structural experiments have found a conformational change involving a hinge-like movement of a surface loop (residues 213-224) which is anticipated to take place upon the binding of the diphosphate moiety of NADPH. The reorientation of this loop, expected to permit the release of NADP+, represents the rate-limiting step of the catalytic mechanism. This study reveals: 1) The Translation/Libration/Screw (TLS) analysis of absolute B-factors of apo AR crystal structures indicates that the 212-224 loop might move as a rigid group. 2) Residues that make the flexible loop slide in the AR binary and ternary complexes. 3) The normalized B-factors separate this segment into three differnt clusters with fewer residues.
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Cite this article as:
Balendiran K. Ganesaratnam, Pandian Rajendran J., Drake Evin, Vinayak Anubhav, Verma Malkhey and Cascio Duilio, B-factor Analysis and Conformational Rearrangement of Aldose Reductase, Current Proteomics 2014; 11 (3) . https://dx.doi.org/10.2174/157016461103140922163444
DOI https://dx.doi.org/10.2174/157016461103140922163444 |
Print ISSN 1570-1646 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6247 |
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