EXAFS OF THE NOVEL HETERO-BINUCLEAR CENTER OF RIBONUCLEOTIDE REDUCTASE FROM C T

Stanford University, Stanford CA

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Abstract

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. The R2 subunit of ribonucleotide reductase(RNR) from the human pathogen Chlamydia trachomatis (Ct) features a Mn/Fe heterobinuclear center that initiates proton coupled electron transfer (PCET). This differs from RNRs of other organisms including humans and E. coli which both feature a diiron center and a tyrosine radical to initiate PCET. Sequence analyses indicate other human pathogens, such as Mycobacterium tuberculosis, have Mn/Fe RNRs. The fact that Mn/Fe heterobinuclear centers are incorporated in human pathogens suggests that there may be a window for new antibacterial action. Development of new antibiotics will be aided by a complete understanding of the structure and mechanism of Ct R2. The proposed research seeks to provide extended x-ray absorption fine structure EXAFS) characterizations of the Ct R2 cofactor in its various oxidation states.