BIOINORGANIC CHEMISTRY A Short Course Second Edition

362 IRON-CONTAINING PROTEINS AND ENZYMES

cofactors (prosthetic groups) that are intimately involved with O 2 activation.
Additional coordination sites attach the iron ion in the porphyrin center to
the protein through cysteine side chains, or they serve to coordinate dioxygen,
NO, oxide anion, water, and other ligands during portions of the catalytic
cycle.
Early experiments identifi ed a low - spin ferric, Fe(III), center in an enzyme
specifi c for the substrate camphor, called P450 cam. The P450 cam enzyme ’ s
metallo - cofactor was identifi ed in the substrate - free resting state by its elec-
tron paramagnetic resonance (EPR) spectrum withg - values of 2.45, 2.26, and
1.91.^33 When the substrate, camphor, was added, the EPR signal changed to
indicate the presence of 60% of the high - spin form with g - values of 7.85, 3.97,
and 1.78 (experiments carried out at 12 K). Cytochrome P450 cam continues to
be one of the most - studied members of the P450 superfamily and is the central
enzyme in a three - component oxidase that converts the 5 - methylene group of
camphor to the 5 - exo alcohol. See Figure 7.12.
In 2005, when several publications discussing cytochrome P450 structure
and function appeared inChemical Reviews , there were 4000+ identifi ed P450
genes encoding the cytochrome P450 superfamily.^34 The collection is annotated
on a website maintained by David Nelson ( http://drnelson.utmem.edu/
CytochromeP450.html ). The Nelson site also details the naming system for this
superfamily; for example, cytochrome Pseudomonas putida P450 CAM in the 101
subfamily carries the designation CYP101, while rabbit CYP2B4 is a member
of the 2B subfamily. More information about the cytochrome P450 superfamily
is found on the http://metallo.scripps.edu/index.html web site.
Cytochrome P450 carries out broad functional roles in biological species.
One role is the metabolism of drugs and so - called xenobiotics (exogenous
compounds not native to the organism). P450 ’ s ability to degrade xenobiotics
makes it potentially useful in bioremediation. P450 ’ s second major role involves
the biosynthesis of steroid hormones — for example, cholesterol and other
critical signaling molecules. The latter role includes fat - soluble vitamin metab-
olism and conversion of polyunsaturated fatty acids to biologically active
molecules. The cytochrome P450 molecule is also believed to be involved in
carcinogenesis.

Figure 7.12 Conversion of camphor to its 5 - exo alcohol counterpart using P450
enzyme.

HH

O

HOH

P450 O

camphor 5-exo-hydroxycamphor

enzyme