This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Our INBRE supported research involves the structural characterization of the zinc sites in a series of metalloenzymes involved in bacterial proliferation. The systems under study include a broad array of metallo-b-lactamases, which confer resistance to penicillin-type antibiotics. Unlike the related serine-active lactamases, the metallo-b-lactamases have no known inhibitors and many of them are plasmid encoded, allowing for facile transfer between bacterial species. Also under study are a series of AHL-lactonases which act in the quorum-sensin pathways of gram-positive bacteria, allowing bacterial colonies to display group behavior. We utilize X-ray absorption spectroscopy to directly interrogate the metal sites in frozen solution, without the need for crystalline material. Our methodology provides access to the native metal ion in enzyme resting states and product complexes, and through rapid freeze quench techniques, key reaction intermediates
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