STRUCTURAL GENOMICS OF CYTOCHROME P450S

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在该计划提案扩展中，要求SSRL束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 1A 2、2A 6、2A 13、2B 1、2B 4、2C 8、2C 9、2C 19、3A 4、Cyp 24 A1、Cyp 46 A1、Cyp 73 A5和Cyp 98 A3。在这些晶体学实验中，共有六个NIH支持的研究项目，重点是P450的结构和功能。使用SSRL光束线可以实现高通量方法，大大提高生产率，并促进研究人员之间的协作和洞察力。细胞色素P450是单氧化反应的通用催化剂，在生物学中广泛存在，包括人类基因组中的约60种不同的酶。这些综合研究代表了结构基因组学方法，解决了蛋白质构象和活性位点相互作用所需的活性和特异性对生物底物和异生素分子的巨大多样性的范围。

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.