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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