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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.