ELECTROSTATIC GUIDANCE IN PROKARYOTIC CU,ZN SUPEROXIDE DISMUTASE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。Cu，Zn超氧化物歧化酶是一种同源二聚体酶，在细胞防御自由基引起的氧化损伤中起重要作用。感染性细菌如N.脑膜炎和B.流产病毒利用这种酶在宿主免疫系统的巨噬细胞和嗜中性粒细胞产生的超氧化物离子的冲击下存活。二聚体界面和决定因素的静电指导的基板不同的原核和真核酶。我们正在研究原核铜，锌超氧化物歧化酶通过定点诱变耦合蛋白质结构测定的X-射线晶体学的静电指导的决定因素。需要同步辐射来获得高分辨率结构，这将导致对原核酶中静电底物引导的详细理解，并可能导致开发新的治疗剂来对抗致命的细菌感染。

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. Cu,Zn superoxide dismutase is a homodimeric enzyme that is central in the cellular defense against oxidative damage due to free radicals. Infectious bacteria such as N. meningitides and B. abortus utilize this enzyme to survive the onslaught of superoxide ions generated by the macrophages and neutrophils of the host's immune system. The dimer interface and the determinants for electrostatic guidance of the substrate differ between the prokaryotic and eukaryotic enzymes. We are studying the determinants for electrostatic guidance in prokaryotic Cu,Zn superoxide dismutase through site-directed mutagenesis coupled to protein structure determination by x-ray crystallography. Synchrotron radiation is required to obtain a high resolution structure which will lead to a detailed understanding of electrostatic substrate guidance in the prokaryotic enzyme, and may lead to the development of novel therapeutic agents to combat fatal bacterial infections.