· large & diverse family of enzymes: ~8000 known, 57 in humans
· found in plants, animals, bacteria, archaea
· all share a common heme + cysS active site
· differing functions, including drug metabolism and biosynthesis of steroids, often acting on multiple substrates
· P450s effect a remarkable selective CH activation reaction: RH + O2 + 2e + 2H+ → ROH + H2O
· as a monooxygenase, P450s require two electrons from additional source; usually, this is NAD(P)H, delivered via reducing protein carrying either an FMN/FAD or a Fd cofactor
Aromatic Amino Acid Hydroxylases
A wide class of similar enzymes, including:
· phenylalanine hydroxylase (PheOH or PAH)
· tyrosine hydroxylase (TyrOH or TOH)
· tryptophan hydroxylase (TrpOH or TPH)
· all AAAHs share a similar activity, tetrameric structure, and identical Fe(his)2(glu) active sites
· require a pterin cofactor to supply two electrons
· different metabolic functions, including aa catabolism, synthetic pathway to L-DOPA, serotonin, etc.
· wide class of large associated protein complexes
· found in soil bacteria
· role in biodegradation of aromatics (PhH PhMe [PhCO2] PhNO2 etc)
· two sites: catalytic non-heme Fe(II) and Rieske et cluster, bridged by Asp
· Fe(NHis)2(OAsp) active site
· electrons from NADH, transferred to active site via Rieske cluster through an intermediate FAD/FeS protein
· regio- and stereoselective cis-dihydroxylations of arenes
· unusual side-on [OOH] intermediate
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