Post on 26-Jan-2016
description
Cytochrome P450 Monooxygenasesubiquitous in nature:> 40 in humans> 250 in plants>400 in rice
signature motif:F—G-R-C-G
requires redox partner
scission of O2
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 Å2
interaction with membrane:
Heme binding domain:
heme-thiolate serves asthe 5th 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:
360Å3 volume
Cyrstal structure confirms mutagenesis studies
Heme iron is 4.8Åfrom 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