ELECTROSTATIC GUIDANCE IN PROKARYOTIC CU,ZN SUPEROXIDE DISMUTASE

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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.