학술논문
B-factor Analysis and Conformational Rearrangement of Aldose Reductase.
Document Type
Academic Journal
Author
Balendiran GK; Department of Chemistry, WBSH 6017, Youngstown State University, One University Plaza, Youngstown, OH 44555.; Pandian JR; Department of Business Administration, College of Business Administration, Gulf University for Science and Technology, Mubarak Al-Abdullah Area/West Mishref, Kuwait.; Drake E; Department of Chemistry, WBSH 6017, Youngstown State University, One University Plaza, Youngstown, OH 44555.; Vinayak A; Department of Chemistry, WBSH 6017, Youngstown State University, One University Plaza, Youngstown, OH 44555.; Verma M; Manchester Institute of Biotechnology, 131 Princess Street, The University of Manchester, Manchester, M1 7DN, UK.; Cascio D; UCLA-DOE, 611 Charles E. Young Drive East, 220 Boyer Hall, Los Angeles, CA 90095, USA.
Source
Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 101208451 Publication Model: Print Cited Medium: Print ISSN: 1570-1646 (Print) Linking ISSN: 15701646 NLM ISO Abbreviation: Curr Proteomics Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
1570-1646
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 different clusters with fewer residues.