Complex Metallocluster Structure and Assembly

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Metal ions in biology allow for an expanded chemical repertoire; the local protein environment and metal coordination sphere act synergistically to confer unique reactivity. It is therefore not surprising that the reactions catalyzed by metalloenzymes are chemically challenging and essential for life. We use X-ray crystallography to study the structure and mechanism of complex metallocofactors. Our findings have applications for the synthesis of biomimetic catalysts and in the design of enzyme inhibitors. In addition to investigating the mechanisms of these enzymes, it is also essential to understand the regulation of the levels of the trace minerals required for metallocenter assembly. Here we propose to study the structure and mechanism of enzymes involved in carbon monoxide oxidation and acetyl-CoA synthesis: the Ni requiring carbon monoxide dehydrogenase/acetyl-CoA synthases (CODH/ACS), corrinoid Fe-S protein (CFeSP), methyltetrahydrofolate-CFeSP methyltransferase (MeTr). To explore cellular Ni uptake, we will investigate the structure and mechanism of Ni-regulatory protein NikR. [unreadable] [unreadable]