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.

中文翻译：

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醛糖还原酶的B因子分析和构象重排

由醛糖还原酶 (AR) 催化的 NADPH 依赖性葡萄糖还原反应遵循顺序有序的动力学机制，其中辅因子 NADPH 在醛底物之前与酶结合。动力学/结构实验发现构象变化涉及表面环（残基 213-224）的铰链状运动，预计在结合 NADPH 的二磷酸部分时发生。该回路的重新定向，预计将允许 NADP+ 的释放，代表催化机制的限速步骤。该研究揭示：1) apo AR 晶体结构的绝对 B 因子的平移/自由/螺旋 (TLS) 分析表明 212-224 环可能作为一个刚性组移动。2) 使柔性环在 AR 二元和三元复合物中滑动的残基。