CRYSTAL STRUCTURE OF A MAMMALIAN REDECTASE

哺乳动物还原酶的晶体结构

• 批准号: 8363403
• 负责人: Lakshmi Sangeetha Vedula
• 金额: $ 0.25万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363403
• 关键词: Bile Acids; Binding; Carbon; Complex; Crystallography; Enzymatic Biochemistry; Funding; Grant; Human; Ketosteroids; Light; NADP; National Center for Research Resources; Oxidoreductase; Principal Investigator; Reaction; Research; Research Infrastructure; Resolution; Resources; Roentgen Rays; Source; Steroids; Structure; Synchrotrons; Testosterone; United States National Institutes of Health; cost; pi bond; steroid hormone

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. Aldo-Keto Reductase (AKR) 1D1 (steroid 5-beta-reductase) catalyzes the conversion of all Delta(4)-3-ketosteroids to form 5-beta-dihydrosteroids, a first step in the clearance of steroid hormones, and an essential step in the synthesis of all bile-acids. The reaction is unique in steroid enzymology since hydride transfer from NADPH yields a A/B-ring cis-configuration producing a 90 degree bend in steroid structure. Recently we determined the X-ray crystal structure of human Delta(4)-3-ketosteroid 5-beta-reductase (AKR1D1) complexed with NADP+ and testosterone at 1.62 ¿ resolution. This structure represents the first crystal structure of a mammalian steroid hormone carbon-carbon double bond reductase. However, the structure revealed that testosterone binds in an unproductive mode. We are looking to determine the structure of AKR1D1 in complex with several substrates that would present

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 醛酮还原酶（AKR）1D 1（类固醇5-β-还原酶）催化所有Delta（4）-3-酮类类固醇转化为5-β-二氢类固醇，这是清除类固醇激素的第一步，也是合成所有胆汁酸的重要步骤。该反应在类固醇酶学中是独特的，因为从NADPH的氢化物转移产生A/B环顺式构型，在类固醇结构中产生90度弯曲。最近，我们确定了人δ（4）-3-酮类类固醇5-β-还原酶（AKR 1D 1）与NADP+和睾酮复合的X射线晶体结构，分辨率为1.62。该结构代表哺乳动物类固醇激素碳-碳双键还原酶的第一个晶体结构。然而，该结构揭示了睾酮以非生产性模式结合。我们正在寻找确定AKR 1D 1与几种底物复合的结构，