STRUCTURAL CHARACTERIZATION OF DE NOVO DESIGNED METALLOPEPTIDE METAL SITES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 从头设计的金属肽提供了简化的结构，保留了足够的复杂性，是有用的金属蛋白模型。特别地，锌碳酸酐酶（CA）和亚硝酸铜还原酶（CuNIR）的模型可以使用在金属结合位点中用组氨酸卷曲的三链螺旋来合成。CA模型已显示出有趣的水解能力对乙酰酯，并可以适当地设计为引入额外的结合位点的金属结构的作用，而不干扰催化活性位点。CuNIR模型已经显示出以与天然蛋白质类似的方式结合一氧化碳的能力。酶的活性，底物结合和金属为中心的氧化还原电位的调谐可以通过不仅在第一球的配位环境，而且在第二球和超越作出系统的变化来调谐。

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.