STRUCTURAL STUDIES ON ENZYMES IMPLICATED IN BACTERIAL ANTIBIOTIC RESISTANCE

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。 我们实验室的总体研究领域涉及与抗生素耐药性有关的细菌酶的生物化学、酶学和结构生物学，主要是那些导致β-内酰胺类和氨基糖苷类抗生素失活的酶。这项关于SSRL束流时间的建议侧重于收集关于天然酶和突变酶以及底物/抑制剂复合体的高分辨率衍射数据。在SSRL收集数据的愿望是基于我们对来自许多不同晶体的高质量、高分辨率衍射数据的需求，其中一些晶体的衍射到原子分辨率，特别是在β-内酰胺酶的情况下。此外，我们现在正在生产我们的大部分蛋白质作为硒-蛋氨酸衍生物，我们预计对收集准确的MAD数据的需求将会增加。

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 general area of research in our laboratory involves the biochemistry, enzymology and structural biology of bacterial enzymes implicated in antibiotic resistance, primarily those enzymes responsible for the deactivation of beta-lactam and aminoglycoside antibiotics. This proposal for beam time at SSRL focuses on the collection of high resolution diffraction data on native and mutant enzymes, and substrate/inhibitor complexes. The desire to collect data at SSRL is based upon our need for high quality, high resolution diffraction data from a number of different crystals, some of which diffract to atomic resolution, particularly in the case of the beta-lactamase enzymes. In addition, we are now producing the majority of our proteins as seleno-methionine derivatives, and we envisage an increased requirement for the collection of accurate MAD data.