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Cytochrome P450s

  HIV crystal collage
Single crystals of microsomal cytochrome P450 CYP2C5.

Cytochrome P450s are membrane bound enzymes and universal catalysts for monooxygenation reactions. They are very widespread in biology and 60 distinct enzymes are coded in the human genome. Sequence variation and plasticity among elements of the protein fold (see figure on the Home page) enable P450s to accommodate a vast array of structurally diverse substrates. Nevertheless, individual P450s are highly regio- and stereospecific enzymes, and exhibit distinct substrate specificity profiles. To address the diversity vs. specificity paradox, and the basis of specificity, we have determined over 40 crystal structures of P450s from different classes, families and subfamilies in complex with substrates or inhibitors, or as the unliganded enzymes. These on-going crystallographic experiments are in collaboration with Eric Johnson (TSRI), James Halpert (UCSD) and Irina Pikuleva (Case Western), and are necessary to understand drug metabolism and design inhibitors of steroid and hormone specific P450s.







HIV Protease

Cytochrome ba3 oxidase

Cytochrome P450s

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