STRUCTURAL CHARACTERIZATION OF DE NOVO DESIGNED METALLOPEPTIDE METAL SITES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 从头设计的金属多肽提供了简化的结构，保留了足够的复杂性，可以作为有用的金属蛋白模型。特别是，锌碳酸酐酶(CA)和亚硝酸铜还原酶(CuNIR)模型可以用金属结合部位的组氨酸缠绕的三链线圈来合成。CA的模型已经显示出对乙酰酯的有趣的水解能力，并且可以适当地设计来为具有结构作用的金属引入额外的结合部位，而不会对催化活性部位产生任何干扰。CuNIR的模型已经显示出以类似于天然蛋白质的方式结合一氧化碳的能力。酶的活性、底物结合和金属中心氧化还原电位的调节不仅可以通过在第一球配位环境中进行系统的改变，也可以在第二球及更远的环境中进行调整。

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.