title: B-factor Analysis and Conformational Rearrangement of Aldose Reductase.
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.
authors.affiliation: Department of Chemistry, WBSH 6017, Youngstown State University, One University Plaza, Youngstown, OH 44555.
authors.forename: Ganesaratnam K
authors.initials: GK
authors.lastname: Balendiran
authors.affiliation: Department of Business Administration, College of Business Administration, Gulf University for Science and Technology, Mubarak Al-Abdullah Area/West Mishref, Kuwait.
authors.forename: J Rajendran
authors.initials: JR
authors.lastname: Pandian
authors.affiliation: Department of Chemistry, WBSH 6017, Youngstown State University, One University Plaza, Youngstown, OH 44555.
authors.forename: Evin
authors.initials: E
authors.lastname: Drake
authors.affiliation: Department of Chemistry, WBSH 6017, Youngstown State University, One University Plaza, Youngstown, OH 44555.
authors.forename: Anubhav
authors.initials: A
authors.lastname: Vinayak
authors.affiliation: Manchester Institute of Biotechnology, 131 Princess Street, The University of Manchester, Manchester, M1 7DN, UK.
authors.forename: Malkhey
authors.initials: M
authors.lastname: Verma
authors.affiliation: UCLA-DOE, 611 Charles E. Young Drive East, 220 Boyer Hall, Los Angeles, CA 90095, USA.
authors.forename: Duilio
authors.initials: D
authors.lastname: Cascio
keywords: Aldo-keto reductase; B-factor; TLS; clustering; crystal structure; statistical analysis; structural dynamics