STRUCTURAL INVESTIGATION OF GLYCOSYLTRANSFERASES

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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. We are interested in understanding the biological function and mechanism of several bacterial and human glycosyltransferases. We have developed methods to express, purify, and kinetically characterize glycosyltransferases that are important for bacterial pathogenesis and human disease. We have also implemented screens to look for inhibitors of some of these glycosyltranferases. These inhibitors can serve as biological probes of these enzymes and could help determine whether these proteins are viable therapeutic targets. An important aspect of this endeavor is to obtain structural information about these targets. A structure for these glycosyltranferases would be invaluable for the purposes of both mechanistic understanding and inhibitor development. We are therefore interested in obtaining structures of these enzymes in the apo form, with substrate bound, and with inhibitors bounds.