| Literature References | 1. NOMENCLATURE COMMITTEE OF THE INTERNATIONAL UNION OF BIOCHEMISTRY
Nomenclature of electron-transfer proteins. Recommendations 1989.
EUR.J.BIOCHEMISTRY 200 599-611 (1991).
2. NEBERT, D.W. AND GONZALEZ, F.J.
P450 genes: structure, evolution, and regulation.
ANNU.REV.BIOCHEMISTRY 56 945-993 (1987).
3. NELSON, D.R., KAMATAKI, T., WAXMAN, D.J., GUENGERICH, F.P., ESTABROOK,
R.W., FEYEREISEN, R., GONZALEZ, F.J., COON, M.J., GUNSALUS, I.C., GOTOH, O.,
OKUDA, K. AND NEBERT, D.W.
The P450 superfamily: update on new sequences, gene mapping, accession
numbers, early trivial names of enzymes, and nomenclature.
DNA CELL BIOL. 12 1-51 (1993).
4. GOTOH, O.
Evolution and differentiation of P-450 genes.
IN BIOCHEMISTRY T., 2ND ED., ISHIMURA, Y. AND FUJII-KURIYAMA, Y., EDS.,
KODANSHA, TOKYO, 1993, PP.255-272.
5. NELSON, D.R.
Cytochrome P450 homepage.
http://drnelson.utmem.edu/CytochromeP450.html
6. NELSON, D.R.
Metazoan Cytochrome P450 evolution.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY PART C 121 15-22 (1998).
7. LEWIS, D.F.V.
P450 substrate specificity and metabolism.
IN CYTOCHROMES P450: STRUCTURE, FUNCTION AND MECHANISM, TAYLOR AND FRANCIS
LTD., LONDON, 1996, PP.115-167.
8. WANG, H., LANZA, D. AND YOST, G.
Cloning and expression of CYP2F3, a cytochrome P450 that bioactivates the
selective pneumotoxins 3-methylindole and naphthalene.
ARCH.BIOCHEM.BIOPHYS. 349 329-340 (1998).
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| Documentation | P450 enzymes constitute a superfamily of haem-thiolate proteins [1], widely
distributed in bacteria, fungi, plants and animals. The enzymes are involved
in metabolism of a plethora of both exogenous and endogenous compounds [2].
Usually, they act as terminal oxidases in multi-component electron-transfer
chains, called P450-containing monooxygenase systems.
Current P450 nomenclature, based on divergent evolution of the P450
superfamily, was proposed and developed by Nebert et al. [3]. On the basis
of sequence similarity, all P450s can be categorised into 2 main classes,
the so-called B- and E-classes: P450 proteins of prokaryotic 3-component
systems and fungal P450nor (CYP55) belong to the B-class; all other known
P450s from distinct systems are of the E-class [4]. E-class P450s may be
further divided into 5 subclasses (groups) according to protein sequence
similarities. The data suggest that divergence of the P450 superfamily
into B- and E-classes, and further divergence into stable P450 groups
within the E-class, must be very ancient and had occured before the
appearance of eukaryotes.
Given the rapid increase in numbers of P450s, Nelson introduced the concept
of a higher-order classification of P450 families into clans [3] based on
sequence similarity. This is similar to the previous grouping into B- and
E-classes; both classifications are still used. According to Nelson's
system, clan 2 contains the CYP2 plus CYP1, 17, 18, 21 and 71 families, and
corresponds to the E-class group I proteins [5,6]. Members of the first 4
families are of vertebrate origin, while those from CYP71 derive from plants.
CYP1 and CYP2 enzymes mainly metabolise exogenous substrates, whereas CYP17
and CYP21 are involved in metabolism of endogenous physiologically-active
compounds.
The CYP2 family, comprising 15 subfamilies (A-H, J-N, P and Q), is the most
dominant in clan 2. Six of these subfamilies are non-mammalian: 2H derives
from chicken; 2K, 2M, 2N and 2P are from fish; 2L is from lobster; and 2Q
from Xenopus [5]. The first five (A-E) are present in mammalian liver, but
in differing amounts and with different inducibilities [7]. Members of the
CYP2F gene subfamily, meanwhile, are selectively expressed in lung tissues,
and have been implicated as important catalysts in the formation of reactive
intermediates from several pneumotoxic chemicals. Human CYP2F1 bioactivates
3-methylindole (3MI), while mouse CYP2F2 bioactivates naphthalene [8].
EP450ICYP2F is a 4-element fingerprint that provides a signature for the
CYP2F P450 family. The fingerprint was derived from an initial alignment of
4 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise the
CYP2F proteins but distinguish them from the rest of the CYP2 family - motifs
1-3 lie in the N-terminal two thirds of the aligment; and motif 4 resides in
the C-terminal region, beyond the haem-binding site. Two iterations on
SPTR55_38f were required to reach convergence, at which point a true set
comprising 8 sequences was identified. A single partial match was also found,
Q32MN5, a translated human cDNA sequence that fails to match motif 4.
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