STRUCTURE-FUNCTION STUDIES ON C-TERMINAL TRUNCATIONS OF 11?-HYDROXYSTEROID

11?-羟基类固醇C端截断的结构功能研究

• 批准号: 7370684
• 负责人: GYORGY SNELL
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370684
• 关键词: STRUCTURE; FUNCTION; STUDIES; TERMINAL; TRUNCATIONS

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. Human 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) is an ER-localized membrane protein that catalyzes the interconversion of cortisone and cortisol. In adipose tissue, excessive cortisol production through 11?-HSD1 activity has been implicated in the pathogenesis of type II diabetes and obesity, which makes this enzyme a potential drug target against these diseases. Recently we have solved the first high-resolution crystal structure of the extracellular portion of the enzyme. We wish to undertake further studies on 11?-HSD1 with regards to enzyme oligomerization and reductase activity. To this end, we would like to carry out systematic truncations of the C-terminus and use x-ray crystallography to understand the structural features controlling these two interrelated functions.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。人类11号？羟类固醇脱氢酶1型（11？- HSD 1）是一种ER定位的膜蛋白，催化可的松和皮质醇的相互转化。在脂肪组织中，通过11？- HSD 1活性与II型糖尿病和肥胖症的发病机制有关，这使得这种酶成为对抗这些疾病的潜在药物靶标。最近，我们已经解决了第一个高分辨率的晶体结构的胞外部分的酶。我们希望进一步研究11？关于酶寡聚化和还原酶活性的HSD 1。为此，我们想进行系统的截断的C-末端，并使用X-射线晶体学来了解控制这两个相互关联的功能的结构特征。