STRUCTURAL CHARACTERIZATION OF DE NOVO DESIGNED METALLOPEPTIDE METAL SITES

从头设计的金属肽金属位点的结构表征

• 批准号: 8362393
• 负责人: James E. Penner-Hahn
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362393
• 关键词: Active Sites; Binding; Carbon Monoxide; Copper; Environment; Esters; Funding; Grant; Histidine; Metal Binding Site; Metalloproteins; Metals; Modeling; National Center for Research Resources; Nitrite Reductase; Oxidation-Reduction; Principal Investigator; Proteins; Radiation; Research; Research Infrastructure; Resources; Role; Site; Source; United States National Institutes of Health; analog; carbonate dehydratase; cost; design; interest; 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. De novo designed metallopeptides offer simplified constructs retaining sufficient complexity to be useful models of metalloproteins. In particular, models of Zn Carbonic Anhydrase (CA) and Copper Nitrite Reductase (CuNIR) can be synthesized using tri-stranded coil coiled with histidines in the metal binding site. Models of CA have shown interesting hydrolitic capabilities towards acetyl esters, and can be properly designed for the introduction of additional binding site for metals with structural roles without any interference with the catalytic active site. Models of CuNIR have shown the capability to bind carbon monoxide in a fashion analogue to that of the natural protein. The tuning of enzymatic activity, substrate binding and metal-centered redox potential can be tuned by making systematic changes in not only the first sphere coordination environment, but also the second sphere and beyond.

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。 从头设计的金属肽提供了简化的构造，它们保留了足够的复杂性，是金属蛋白的有用模型。特别是，可以使用金属结合位点中的三链卷轴盘绕，锌含碳酸酐酶（Ca）和铜亚硝酸盐还原酶（CUNIR）的模型可以合成。 CA的模型显示了对乙酰酯的有趣水解能力，并且可以适当设计用于引入具有结构作用的金属的其他结合位点，而不会与催化活性位点进行任何干扰。 Cunir的模型表明能够以一种与天然蛋白质的方式结合一氧化碳的能力。可以通过在第一个球体协调环境中进行系统的变化来调整酶活性，底物结合和以金属为中心的氧化还原电位的调整，还可以调节第二球及以后的系统变化。