OLIGOMERIZATION STATE OF THE MONOAMINE OXIDASES

单胺氧化酶的低聚状态

• 批准号: 8363971
• 负责人: PETER P BORBAT
• 金额: $ 0.05万
• 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: 2011-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363971
• 关键词: Active Sites; Amines; Binding; Data; Enzymes; Funding; Grant; Human; Measurement; Membrane; Monoamine Oxidase; Monoamine Oxidase A; Mutation; National Center for Research Resources; Outer Mitochondrial Membrane; Pargyline; Play; Positioning Attribute; Principal Investigator; Rattus; Research; Research Infrastructure; Resources; Role; Sampling; Source; Spin Labels; Structure; Study models; Technology; Testing; United States National Institutes of Health; analog; cost; inhibitor/antagonist; mutant; neurotransmitter metabolism; quantum

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. Monoamine oxidases ( A & B) are outer mitochondrial membrane-bound enzymes that play important roles in amine neurotransmitter metabolism. Sequence and modeling studies suggest human MAO A differs from all other mammalian MAO A in that it is monomeric rather than dimeric in the outer membrane due to a Glu151Lys mutation. Crystal structures of purified human and rat MAO A provide additional support for this hypothesis. To provide a direct experimental test, analogues of the inhibitor pargyline with a nitroxide spin label on the para position will be synthesized and covalently incorporated into the active sites of human and rat MAO A, the Lys151Glu mutant of human MAO A, and human MAO B. Structural data of the dimeric form of crystalline human MAO B show the distance between the active site cavities is 42 ¿. This distance is readily determined by Double Quantum Coherence EPR measurements on these samples. The dipolar spectral data will provide distance information that will determine if these enzyme species are in their dimeric or monomeric forms in the mitochondrial outer membrane.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 单胺氧化物（A＆B）是线粒体膜结合的酶，在胺神经递质代谢中起重要作用。序列和建模研究表明，人Mao与所有其他哺乳动物MAO A不同，因为它是由于GLU151LYS突变而导致的外膜中的单体而不是二聚体。纯化的人和大鼠毛的晶体结构为这一假设提供了额外的支持。为了提供直接的实验测试，将合成抑制剂帕尔吉林与氮氧化物自旋标记的类似物，并将共价合成并共价纳入人类和大鼠Mao A的活性位点，Lys151Glu突变体，人MaO A的lys151Glu突变体，人Mao B.人Mao B. Crystalline Mao Mao Mao Ma Ma Ma的diecteric b。这些距离很容易通过这些样品上的双量子相干性EPR测量来确定。偶极光谱数据将提供距离信息，以确定这些酶种类是否在线粒体外膜的二聚体或单体形式中。