STRUCTURAL INVESTIGATION OF GLYCOSYLTRANSFERASES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们有兴趣了解几种细菌和人类糖基转移酶的生物学功能和机制。我们已经开发了表达、纯化和动力学表征糖基转移酶的方法，这些糖基转移酶在细菌发病机制和人类疾病中是重要的。我们还进行了筛选，以寻找其中一些糖基转移酶的抑制剂。这些抑制剂可以作为这些酶的生物探针，并可以帮助确定这些蛋白质是否是可行的治疗靶点。这一努力的一个重要方面是获得关于这些目标的结构信息。这些糖基转移酶的结构对于机制的理解和抑制剂的开发都是非常有价值的。因此，我们对获得载脂蛋白形式、底物结合和抑制剂结合的这些酶的结构感兴趣。

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.