STRUCTURAL GENOMICS OF CYTOCHROME P450S

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。 在本计划提案中，要求SSRL束流时间继续对微粒体和线粒体细胞色素P450的晶体结构进行实验，包括P450 1A2、2A6、2A13、2B1、2B4、2C8、2C9、2C19、3A4、CYP24A1、Cyp46A1、Cyp73A5和Cyp98A3。在这些结晶学实验中，总共有六个由美国国立卫生研究院资助的研究项目，重点是P450的结构和功能。使用SSRL光束线可以实现高吞吐量方法，极大地提高生产率，并促进调查人员之间的合作和洞察力。细胞色素P450是单氧合反应的通用催化剂，广泛存在于生物学中，包括人类基因组中的60种不同的酶。这些联合研究代表了一种结构基因组学方法，解决了蛋白质构象和活性部位相互作用的范围，这些活性和特异性是针对巨大多样性的生物底物和外源分子所需的。

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. In this program proposal extension, SSRL beam time is requested to continue experiments on the crystal structures of microsomal and mitochondrial cytochrome P450s, including P450s 1A2, 2A6, 2A13, 2B1, 2B4, 2C8, 2C9, 2C19, 3A4, Cyp24A1, Cyp46A1, Cyp73A5, and Cyp98A3. Together, six NIH supported research projects, focused on P450 structure and function, are represented in these crystallographic experiments. Access to SSRL beam lines allows a high throughput approach, greatly enhancing productivity, and fostering collaboration and insight among the investigators. Cytochrome P450s are universal catalysts for monoxygenation reactions and are widespread in biology, including ~60 distinct enzymes in the human genome. These combined studies represent a structural genomics approach, addressing the range of protein conformations and active site interactions required for activity and specificity toward an immense diversity of biological substrates and xenobiotic molecules.