DB code: S00030

CATH domain 1.10.630.10 : Cytochrome p450 Catalytic domain
E.C. 1.14.14.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.630.10 : Cytochrome p450 S00033 S00031 M00154

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P00179 Cytochrome P450 2C5
EC 1.14.14.1
CYPIIC5
P450 1
Progesterone 21-hydroxylase
P450IIC5
NP_001164397.1 (Protein)
NM_001170926.1 (DNA/RNA sequence)
PF00067 (p450)
[Graphical View]

KEGG enzyme name
unspecific monooxygenase
microsomal monooxygenase
xenobiotic monooxygenase
aryl-4-monooxygenase
aryl hydrocarbon hydroxylase
microsomal P-450
flavoprotein-linked monooxygenase
flavoprotein monooxygenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00179 CP2C5_RABIT RH + reduced flavoprotein + O(2) = ROH + oxidized flavoprotein + H(2)O. Endoplasmic reticulum membrane (By similarity). Microsome membrane (By similarity). Heme group.

KEGG Pathways
Map code Pathways E.C.
MAP00071 Fatty acid metabolism
MAP00150 Androgen and estrogen metabolism
MAP00232 Caffeine metabolism
MAP00361 gamma-Hexachlorocyclohexane degradation
MAP00380 Tryptophan metabolism
MAP00590 Arachidonic acid metabolism
MAP00591 Linoleic acid metabolism
MAP00830 Retinol metabolism
MAP00980 Metabolism of xenobiotics by cytochrome P450
MAP00982 Drug metabolism - cytochrome P450
MAP00983 Drug metabolism - other enzymes

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00032 C03024 C00007 C01371 C00162 C01598 C03161 C00001 C01335 C05102 C05643
E.C.
Compound Heme Reduced flavoprotein O2 RH Fatty acid Melatonin Oxidized flavoprotein H2O ROH alpha-Hydroxy fatty acid 6-Hydroxymelatonin
Type aromatic ring (with nitrogen atoms),carboxyl group,heavy metal amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),peptide/protein others lipid fatty acid amide group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms) amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),peptide/protein H2O lipid carbohydrate,fatty acid amide group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms)
ChEBI 17627
 26355
 17627
 26355
 		15379
 26689
 27140
 15379
 26689
 27140
 		16796
 16796
 		15377
 15377
 		2198
 2198
PubChem 977
 977
 		896
 896
 		22247451
 962
 22247451
 962
 		1864
 1864
1dt6A Bound:HEM Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1n6bA Bound:HEM Unbound Unbound Bound:DMZ Unbound Unbound Unbound Unbound Unbound Unbound
1nr6A Bound:HEM Unbound Unbound Unbound Unbound Analogue:DIF Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00179

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dt6A THR 298 CYS 432(Heme iron binding) mutant D2A, H24S, G25S, N202H, R206E, I207L, S209G, S210T
1n6bA THR 298 CYS 432(Heme iron binding)
1nr6A THR 298 CYS 432(Heme iron binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.10, Fig.11, Fig.12, p.1076-1078 3
[10]
Fig. 1, Fig.7

References
[1]
Resource
Comments
Medline ID
PubMed ID 1524428
Journal Arch Biochem Biophys
Year 1992
Volume 298
Pages 198-203
Authors Krainev AG, Shimizu T, Hiroya K, Hatano M
Title Effect of mutations at Lys250, Arg251, and Lys253 of cytochrome P450 1A2 on the catalytic activities and the bindings of bifunctional axial ligands.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7549871
Journal Protein Sci
Year 1995
Volume 4
Pages 1065-80
Authors Graham-Lorence S, Amarneh B, White RE, Peterson JA, Simpson ER
Title A three-dimensional model of aromatase cytochrome P450.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7645302
Journal Xenobiotica
Year 1995
Volume 25
Pages 333-66
Authors Lewis DF
Title Three-dimensional models of human and other mammalian microsomal P450s constructed from an alignment with P450102 (P450bm3).
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8902262
Journal Chem Res Toxicol
Year 1996
Volume 9
Pages 1079-91
Authors de Groot MJ, Vermeulen NP, Kramer JD, van Acker FA, Donne-Op den Kelder GM
Title A three-dimensional protein model for human cytochrome P450 2D6 based on the crystal structures of P450 101, P450 102, and P450 108.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8830036
Journal J Biochem (Tokyo)
Year 1996
Volume 119
Pages 435-40
Authors Nakayama N, Takemae A, Shoun H
Title Cytochrome P450foxy, a catalytically self-sufficient fatty acid hydroxylase of the fungus Fusarium oxysporum.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9141236
Journal Xenobiotica
Year 1997
Volume 27
Pages 287-99
Authors Tan Y, White SP, Paranawithana SR, Yang CS
Title A hypothetical model for the active site of human cytochrome P4502E1.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 9681992
Journal Arch Biochem Biophys
Year 1998
Volume 356
Pages 63-70
Authors Fisher MB, Thompson SJ, Ribeiro V, Lechner MC, Rettie AE
Title P450-catalyzed in-chain desaturation of valproic acid: isoform selectivity and mechanism of formation of Delta 3-valproic acid generated by baculovirus-expressed CYP3A1.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 9737862
Journal Biochemistry
Year 1998
Volume 37
Pages 12847-51
Authors Zheng YM, Fisher MB, Yokotani N, Fujii-Kuriyama Y, Rettie AE
Title Identification of a meander region proline residue critical for heme binding to cytochrome P450: implications for the catalytic function of human CYP4B1.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 9744519
Journal J Steroid Biochem Mol Biol
Year 1998
Volume 66
Pages 217-33
Authors Lewis DF, Lee-Robichaud P
Title Molecular modelling of steroidogenic cytochromes P450 from families CYP11, CYP17, CYP19 and CYP21 based on the CYP102 crystal structure.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10446146
Journal J Biol Chem
Year 1999
Volume 274
Pages 23833-40
Authors Bell-Parikh LC, Guengerich FP
Title Kinetics of cytochrome P450 2E1-catalyzed oxidation of ethanol to acetic acid via acetaldehyde.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10644712
Journal J Biol Chem
Year 2000
Volume 275
Pages 2545-53
Authors Cosme J, Johnson EF
Title Engineering microsomal cytochrome P450 2C5 to be a soluble, monomeric enzyme. Mutations that alter aggregation, phospholipid dependence of catalysis, and membrane binding.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10995755
Journal J Biol Chem
Year 2000
Volume 275
Pages 39734-40
Authors Kitazume T, Takaya N, Nakayama N, Shoun H
Title Fusarium oxysporum fatty-acid subterminal hydroxylase (CYP505) is a membrane-bound eukaryotic counterpart of Bacillus megaterium cytochrome P450BM3.
Related PDB
Related UniProtKB
[13]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS)
Medline ID 20142664
PubMed ID 10678174
Journal Mol Cell
Year 2000
Volume 5
Pages 121-31
Authors Williams PA, Cosme J, Sridhar V, Johnson EF, McRee DE
Title Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity.
Related PDB 1dt6
Related UniProtKB P00179
[14]
Resource
Comments
Medline ID
PubMed ID 10659948
Journal Xenobiotica
Year 2000
Volume 30
Pages 1-25
Authors Lewis DF, Bird MG, Dickins M, Lake BG, Eddershaw PJ, Tarbit MH, Goldfarb PS
Title Molecular modelling of human CYP2E1 by homology with the CYP102 haemoprotein domain: investigation of the interactions of substrates and inhibitors within the putative active site of the human CYP2E1 isoform.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 12237221
Journal J Inorg Biochem
Year 2002
Volume 91
Pages 542-53
Authors Vatsis KP, Peng HM, Coon MJ
Title Replacement of active-site cysteine-436 by serine converts cytochrome P450 2B4 into an NADPH oxidase with negligible monooxygenase activity.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12767218
Journal Biochemistry
Year 2003
Volume 42
Pages 6370-9
Authors Wester MR, Johnson EF, Marques-Soares C, Dansette PM, Mansuy D, Stout CD
Title Structure of a substrate complex of mammalian cytochrome P450 2C5 at 2.3 A resolution: evidence for multiple substrate binding modes.
Related PDB 1n6b
Related UniProtKB P00179
[17]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12899620
Journal Biochemistry
Year 2003
Volume 42
Pages 9335-45
Authors Wester MR, Johnson EF, Marques-Soares C, Dijols S, Dansette PM, Mansuy D, Stout CD
Title Structure of mammalian cytochrome P450 2C5 complexed with diclofenac at 2.1 A resolution: evidence for an induced fit model of substrate binding.
Related PDB 1nr6
Related UniProtKB

Comments
This enzyme belongs to the cytochrome P450 family.
According to the literature [2] and [10], this enzyme catalyzes the following reactions:
(A) Electron transfer from reduced flavoprotein to the heme of this enzyme:
(B) Oxygenation of substrate by O2, producing hydroxylated product and water (H2):

Created Updated
2004-10-20 2009-03-11