STRUCTURE-FUNCTION STUDIES ON C-TERMINAL TRUNCATIONS OF 11BHYDROXYSTERIOD DEHYDR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 人11 β-羟基类固醇脱氢酶1型（11 β-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 β-HSD 1活性产生的过量皮质醇与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。我们希望对11 β-HSD 1的酶寡聚化和还原酶活性进行进一步研究。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。

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 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an ER-localized membrane protein that catalyzes the interconversion of cortisone and cortisol. In adipose tissue, excessive cortisol production through 11beta-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 11beta-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.