STRUCTURAL GENOMICS OF CYTOCHROME P450S

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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. 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.