Cytochrome P450 Monooxygenases ubiquitous in nature: > 40 in humans > 250 in plants >400 in rice signature motif: F—G-R-C-G requires redox partner scission.

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Presentation transcript:

Cytochrome P450 Monooxygenases ubiquitous in nature: > 40 in humans > 250 in plants >400 in rice signature motif: F—G-R-C-G requires redox partner scission of O 2

cytochrome P450 monooxygenase 2C5: Though low sequence identity among cytochromes P450, overall topology is conserved.

Williams et al., Journal of Inorganic Biochemistry 81 (2002) -red regions indicate predicted sites of membrane interaction as predicted by antipeptide antibody binding data -insertion area for CYP2B4: 680 ± 95 Å 2 interaction with membrane:

Heme binding domain:

heme-thiolate serves as the 5 th ligand to the iron Arg430, Trp120, and Arg124 forms H-bonds to the proprionate side chains Thr298 involved in proton relay system

Williams et al., Journal of Inorganic Biochemistry 81 (2002) Substrate binding pocket: 360Å 3 volume Cyrstal structure confirms mutagenesis studies Heme iron is 4.8Å from site of hydroxylation

Interactions of cytochromes P450 with CPR: Method: -look for residues that are conserved among P450s -map these residues onto CYP2C5 The proximal face of enzyme contains majority of the conserved residues,most of which are basic residues distal face proximal face