STUDIES ON STRUCTURAL HOMOLOGUES, PUTIDAREDOXIN REDUCTASE & APOPTOSIS INDUCING F

腐胺氧还蛋白还原酶结构同系物的研究

• 批准号: 7370370
• 负责人: Irina F Sevrioukova
• 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/7370370
• 关键词: STUDIES; STRUCTURAL; HOMOLOGUES; PUTIDAREDOXIN; REDUCTASE

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. A crystallographic approach will be used to determine three-dimensional structures and study structure/function relationships in two structurally homologous FAD-containing enzymes, putidaredoxin reductase (Pdr) from Pseudomonas putida and apoptosis inducing factor (AIF) from mice. Both flavoproteins have a glutathione reductase fold and are bifunctional. Pdr catalyzes electron transfer from NADH to an iron-sulfur protein, putidaredoxin, in cytochrome P450cam monooxygenase, but it also has redox active cysteines and can function as dithiol/disulfide oxidoreduction. AIF is a phylogenetically old mammalian, caspase-independent death effector which, upon apoptosis induction, translocates from its normal localization, the mitochondrial intermembrane space, to the nucleus where it causes chromatin condensation and DNA fragmentation. Neither physiological function nor mechanism of apoptosis induced by this protein is known. Our research addresses the question of how the structures of Pdr and AIF are related to their catalytic function.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。晶体学方法将用于确定两种结构同源的含有 FAD 的酶（来自恶臭假单胞菌的恶臭氧还蛋白还原酶（Pdr）和来自小鼠的凋亡诱导因子（AIF））的三维结构并研究结构/功能关系。两种黄素蛋白都具有谷胱甘肽还原酶折叠并且具有双功能。 Pdr 在细胞色素 P450cam 单加氧酶中催化从 NADH 到铁硫蛋白 Putidaredoxin 的电子转移，但它也具有氧化还原活性半胱氨酸，并且可以起到二硫醇/二硫键氧化还原的作用。 AIF 是一种系统发育古老的哺乳动物、不依赖 caspase 的死亡效应物，在诱导细胞凋亡时，从其正常定位（线粒体膜间隙）转移到细胞核，导致染色质浓缩和 DNA 片段化。该蛋白诱导细胞凋亡的生理功能和机制尚不清楚。我们的研究解决了 Pdr 和 AIF 的结构如何与其催化功能相关的问题。