PROTEIN ELECTROSTATICS AND DYNAMICS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这次合作的目标是确定WT hALR2/含腈抑制剂/NADP+的三元络合物的晶体结构。HALR2，人醛糖还原酶，是一种36 kDa的醛酮还原酶，催化碳水化合物代谢产生的醛转化为相应的醇，被认为是导致许多长期糖尿病并发症的原因。我们一直致力于使用含腈的hALR2抑制剂作为斯塔克探针，以研究hALR2中的静电环境。这种三元络合物的晶体结构将被用来定位丁腈探针，并进一步进行分子动力学模拟。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this collaboration is to determine the crystal structure of the tertiary complex of WT hALR2 / nitrile-containing inhibitor / NADP+. hALR2, human aldose reductase, is a 36 kDa aldo-keto reductase that catalyzes the conversion of aldehydes derived from carbohydrate metabolism to corresponding alcohols and is believed to be responsible for many long-term diabetic complications. We have been working on using nitrile-containing hALR2 inhibitors as Stark probes in order to study the electrostatic environment in hALR2. The crystal structure of this tertiary complex will be used to locate the nitrile probe, and to further perform molecular dynamics simulations.