CRYSTAL STRUCUTURE STUDIES OF OCRL

OCRL的晶体结构研究

• 批准号: 8363538
• 负责人: Yuxin Mao
• 金额: $ 0.9万
• 依托单位: CORNELL UNIVERSITY
• 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/8363538
• 关键词: American Society of Hematology; C-terminal; Disease; Fanconi Syndrome; Funding; Grant; Kidney; Link; Mental Retardation; Molecular; N-terminal; National Center for Research Resources; Oculocerebrorenal Syndrome; PH Domain; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Side; Source; Structure; Tertiary Protein Structure; United States National Institutes of Health; congenital cataract; cost; enzyme mechanism; human disease; inositol-1,4,5-trisphosphate 5-phosphatase; insight; mutant; phosphoinositide-3,4,5-triphosphate

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. OCRL was originally identified as the product of the gene responsible for the OculoCerebroRenal syndrome of Lowe. The Lowe syndrome is an X-linked disorder involving congenital cataracts, mental retardation, and renal Fanconi syndrome. OCRL is a multi-domain protein comprising a central inositol 5-phosphatase domain that favours PI(4,5)P2 and PI(3,4,5)P3 as substrates. This domain is flanked at its C-terminal side by an ASH and a catalytically inactive RhoGAP-like domain and an N-terminal PH domain. We recently determined the x-ray structure of the termimal ASH and RhoGAP tandem domains and the NMR structure of the N-terminal PH domian. We are now aimed to determine the structure of OCRL mutants that related to human disease. We have obtained crystals of severl mutants. We expect by determination of the structure of OCRL mutants, we will gain insights on the molecular mechanism of this enzyme.

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。 OCRL最初被确定为导致眼脑肾综合征的基因产物。Lowe综合征是一种X连锁疾病，涉及先天性白内障、智力低下和肾范可尼综合征。 OCRL是一种多结构域蛋白，其包含有利于PI（4，5）P2和PI（3，4，5）P3作为底物的中央肌醇5-磷酸酶结构域。该结构域在其C-末端侧由ASH和无催化活性的RhoGAP样结构域和N-末端PH结构域侧接。 我们最近确定了X射线结构的termendash和RhoGAP串联结构域和NMR结构的N-末端PH结构域。我们的目标是确定与人类疾病相关的OCRL突变体的结构。我们得到了几个变种人的晶体。我们期望通过对OCRL突变体结构的测定，对该酶的分子机制有更深入的了解。