STRUCTURAL ANALYSIS OF NAT

NAT结构分析

• 批准号: 7721637
• 负责人: Kylie J. Walters
• 金额: $ 0.26万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721637
• 关键词: Acetylation; Arylamine N-Acetyltransferase; Catalysis; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA; Funding; Genetic Polymorphism; Grant; Hamsters; Heterocyclic Amines; Homologous Gene; Human; Individual; Institution; Isoenzymes; Longevity; NAT2 gene; NMR Spectroscopy; Pathway interactions; Personal Satisfaction; Predisposition; Proteins; Research; Research Personnel; Resources; Role; Source; Substrate Specificity; System; Ubiquitin; United States National Institutes of Health; cancer type; human NAT2 protein; multicatalytic endopeptidase complex

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. We are studying why certain arylamine N-acetyltransferase (NAT) polymorphisms result in proteins that are not acetylated. NATs are well known for their role in catalyzing either N- or O-acetylation of substrate compounds, including heterocyclic amines. Individual humans possess differences in the DNA that encodes either of their two NAT homologues: NAT1 and NAT2. Certain polymorphisms are associated with predisposition towards specific cancer types and result in proteins with reduced enzymatic activity and cellular abundance. Importantly NAT1 isozymes with such reduced activity are not acetylated and are rapidly ubiquitylated in cells. The ubiquitin-proteasome pathway is well renowned for its role in controlling protein lifespans via degradation. A general regulatory role may exist for this system in NAT catalysis as suggested by the finding that non-acetylated but not acetylated human NAT1 is ubiquitylated in cells. We are studying by NMR spectroscopy hamster NAT2. Hamster NAT2 shares substrate specificity and 81% sequence identity with human NAT1 and is amenable to structural studies by NMR.

这个子项目是众多研究子项目之一