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，不一定是研究者所在机构。晶体学方法将被用来确定三维结构和研究结构/功能的关系，在两个结构上同源的FAD含酶，putidaredoxin还原酶（PDR）从恶臭假单胞菌和凋亡诱导因子（AIF）从小鼠。两种黄素蛋白都有谷胱甘肽还原酶折叠，并且是双功能的。Pdr催化细胞色素P450 cam单加氧酶中从NADH到铁硫蛋白putidaredoxin的电子转移，但它也具有氧化还原活性的半胱氨酸，并可以起到二硫醇/二硫化物氧化还原的作用。AIF是一种遗传学上古老的哺乳动物、半胱天冬酶非依赖性死亡效应物，其在凋亡诱导后从其正常定位（线粒体膜间隙）易位至细胞核，在细胞核中其引起染色质凝聚和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。