CRYSTALLOGRAPHIC ANALYSIS OF A BACTERIAL MEMBRANE PROTEASE

细菌膜蛋白酶的晶体分析

• 批准号: 8361662
• 负责人: YA HA
• 金额: $ 0.55万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361662
• 关键词: Cleaved cell; Data; Disease; Family; Funding; Genes; Grant; Homologous Gene; Light; Membrane; Mutation; National Center for Research Resources; Peptide Hydrolases; Peptides; Principal Investigator; Research; Research Infrastructure; Resources; Source; Specificity; Structure; United States National Institutes of Health; cost; familial Alzheimer disease; presenilin; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Most dominant mutations that cause Familial Alzheimer's Disease (AD) are found in the two homologous presenilin (PS1, PS2) genes. Little is currently known about the structure and mechanism for the presenilin family of proteases. We plan to solve the crystal structure of a bacterial homolog of presenilin. The structural data is likely to shed light on a number of important questions: (i) How does presenilin cleave peptide bonds that appear to be buried in the membrane? (ii) The disease mutations are found throughout the primary sequence pf PS1 and PS2. How do they all alter the cleavage specificity in favor of the more toxic A¿42?

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供 该子项目的主要支持。 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源的子项目可能列出的总成本。 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 导致家族性阿尔茨海默病 (AD) 的大多数显性突变存在于两个同源早老素 (PS1、PS2) 基因中，目前对早老素蛋白酶家族的结构和机制知之甚少。早老素的细菌同系物。结构数据可能揭示许多重要问题：（i）早老素如何裂解似乎埋在膜中的肽键？ (ii) 在 PS1 和 PS2 的整个一级序列中都发现了疾病突变，它们如何改变切割特异性以支持毒性更强的 A？ 42？