CRYSTAL STRUCUTURE STUDIES OF OCRL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 OCRL最初被认为是导致LOWE眼脑肾综合征的基因的产物。Lowe综合征是一种X连锁疾病，涉及先天性白内障、智力低下和肾脏Fanconi综合征。 OCRL是一种多结构域蛋白质，含有一个以PI(4，5)P2和PI(3，4，5)P3为底物的肌醇5-磷酸酶结构域。该结构域在其C-末端两侧有一个ASH和一个催化失活的RhoGAP样结构域和一个N-末端PH结构域。 我们最近测定了末端ASH和RhoGAP串联结构域的X射线结构和N-末端PH结构域的核磁共振结构。我们现在的目标是确定与人类疾病相关的OCRL突变体的结构。我们已经获得了几个突变体的晶体。我们期望通过确定OCRL突变体的结构，我们将对该酶的分子机制有更深入的了解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.