EzCatDB: S00030
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DB codeS00030
CATH domainDomain 11.10.630.10 : Cytochrome p450Catalytic domain
E.C.1.14.14.1

CATH domainRelated DB codes (homologues)
1.10.630.10 : Cytochrome p450S00033,S00031,M00154

Enzyme Name
UniProtKBKEGG

P00179
Protein nameCytochrome P450 2C5unspecific monooxygenase
microsomal monooxygenase
xenobiotic monooxygenase
aryl-4-monooxygenase
aryl hydrocarbon hydroxylase
microsomal P-450
flavoprotein-linked monooxygenase
flavoprotein monooxygenase
SynonymsEC 1.14.14.1
CYPIIC5
P450 1
Progesterone 21-hydroxylase
P450IIC5
RefSeqNP_001164397.1 (Protein)
NM_001170926.1 (DNA/RNA sequence)
PfamPF00067 (p450)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00071Fatty acid metabolism
MAP00150Androgen and estrogen metabolism
MAP00232Caffeine metabolism
MAP00361gamma-Hexachlorocyclohexane degradation
MAP00380Tryptophan metabolism
MAP00590Arachidonic acid metabolism
MAP00591Linoleic acid metabolism
MAP00830Retinol metabolism
MAP00980Metabolism of xenobiotics by cytochrome P450
MAP00982Drug metabolism - cytochrome P450
MAP00983Drug metabolism - other enzymes

UniProtKB:Accession NumberP00179
Entry nameCP2C5_RABIT
ActivityRH + reduced flavoprotein + O(2) = ROH + oxidized flavoprotein + H(2)O.
Subunit
Subcellular locationEndoplasmic reticulum membrane (By similarity). Microsome membrane (By similarity).
CofactorHeme group.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00032C03024C00007C01371C00162C01598C03161C00001C01335C05102C05643
CompoundHemeReduced flavoproteinO2RHFatty acidMelatoninOxidized flavoproteinH2OROHalpha-Hydroxy fatty acid6-Hydroxymelatonin
Typearomatic ring (with nitrogen atoms),carboxyl group,heavy metalamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),peptide/proteinotherslipidfatty acidamide 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/proteinH2Olipidcarbohydrate,fatty acidamide group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms)
ChEBI17627
26355

27140
26689
15379


16796

15377


2198
PubChem

977


896

962
22247451


1864
                   
1dt6ABound:HEMUnboundUnboundUnboundUnboundUnboundUnbound UnboundUnboundUnbound
1n6bABound:HEMUnboundUnboundBound:DMZUnboundUnboundUnbound UnboundUnboundUnbound
1nr6ABound:HEMUnboundUnboundUnboundUnboundAnalogue:DIFUnbound UnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P00179
pdbCatalytic residuesCofactor-binding residuescomment
           
1dt6ATHR 298
CYS 432(Heme iron binding)
mutant D2A, H24S, G25S, N202H, R206E, I207L, S209G, S210T
1n6bATHR 298
CYS 432(Heme iron binding)
 
1nr6ATHR 298
CYS 432(Heme iron binding)
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig.10, Fig.11, Fig.12, p.1076-10783
[10]Fig. 1, Fig.7

references
[1]
PubMed ID1524428
JournalArch Biochem Biophys
Year1992
Volume298
Pages198-203
AuthorsKrainev AG, Shimizu T, Hiroya K, Hatano M
TitleEffect of mutations at Lys250, Arg251, and Lys253 of cytochrome P450 1A2 on the catalytic activities and the bindings of bifunctional axial ligands.
[2]
PubMed ID7549871
JournalProtein Sci
Year1995
Volume4
Pages1065-80
AuthorsGraham-Lorence S, Amarneh B, White RE, Peterson JA, Simpson ER
TitleA three-dimensional model of aromatase cytochrome P450.
[3]
PubMed ID7645302
JournalXenobiotica
Year1995
Volume25
Pages333-66
AuthorsLewis DF
TitleThree-dimensional models of human and other mammalian microsomal P450s constructed from an alignment with P450102 (P450bm3).
[4]
PubMed ID8902262
JournalChem Res Toxicol
Year1996
Volume9
Pages1079-91
Authorsde Groot MJ, Vermeulen NP, Kramer JD, van Acker FA, Donne-Op den Kelder GM
TitleA three-dimensional protein model for human cytochrome P450 2D6 based on the crystal structures of P450 101, P450 102, and P450 108.
[5]
PubMed ID8830036
JournalJ Biochem (Tokyo)
Year1996
Volume119
Pages435-40
AuthorsNakayama N, Takemae A, Shoun H
TitleCytochrome P450foxy, a catalytically self-sufficient fatty acid hydroxylase of the fungus Fusarium oxysporum.
[6]
PubMed ID9141236
JournalXenobiotica
Year1997
Volume27
Pages287-99
AuthorsTan Y, White SP, Paranawithana SR, Yang CS
TitleA hypothetical model for the active site of human cytochrome P4502E1.
[7]
PubMed ID9681992
JournalArch Biochem Biophys
Year1998
Volume356
Pages63-70
AuthorsFisher MB, Thompson SJ, Ribeiro V, Lechner MC, Rettie AE
TitleP450-catalyzed in-chain desaturation of valproic acid: isoform selectivity and mechanism of formation of Delta 3-valproic acid generated by baculovirus-expressed CYP3A1.
[8]
PubMed ID9737862
JournalBiochemistry
Year1998
Volume37
Pages12847-51
AuthorsZheng YM, Fisher MB, Yokotani N, Fujii-Kuriyama Y, Rettie AE
TitleIdentification of a meander region proline residue critical for heme binding to cytochrome P450: implications for the catalytic function of human CYP4B1.
[9]
PubMed ID9744519
JournalJ Steroid Biochem Mol Biol
Year1998
Volume66
Pages217-33
AuthorsLewis DF, Lee-Robichaud P
TitleMolecular modelling of steroidogenic cytochromes P450 from families CYP11, CYP17, CYP19 and CYP21 based on the CYP102 crystal structure.
[10]
PubMed ID10446146
JournalJ Biol Chem
Year1999
Volume274
Pages23833-40
AuthorsBell-Parikh LC, Guengerich FP
TitleKinetics of cytochrome P450 2E1-catalyzed oxidation of ethanol to acetic acid via acetaldehyde.
[11]
PubMed ID10644712
JournalJ Biol Chem
Year2000
Volume275
Pages2545-53
AuthorsCosme J, Johnson EF
TitleEngineering microsomal cytochrome P450 2C5 to be a soluble, monomeric enzyme. Mutations that alter aggregation, phospholipid dependence of catalysis, and membrane binding.
[12]
PubMed ID10995755
JournalJ Biol Chem
Year2000
Volume275
Pages39734-40
AuthorsKitazume T, Takaya N, Nakayama N, Shoun H
TitleFusarium oxysporum fatty-acid subterminal hydroxylase (CYP505) is a membrane-bound eukaryotic counterpart of Bacillus megaterium cytochrome P450BM3.
[13]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS)
Medline ID20142664
PubMed ID10678174
JournalMol Cell
Year2000
Volume5
Pages121-31
AuthorsWilliams PA, Cosme J, Sridhar V, Johnson EF, McRee DE
TitleMammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity.
Related PDB1dt6
Related UniProtKBP00179
[14]
PubMed ID10659948
JournalXenobiotica
Year2000
Volume30
Pages1-25
AuthorsLewis DF, Bird MG, Dickins M, Lake BG, Eddershaw PJ, Tarbit MH, Goldfarb PS
TitleMolecular 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.
[15]
PubMed ID12237221
JournalJ Inorg Biochem
Year2002
Volume91
Pages542-53
AuthorsVatsis KP, Peng HM, Coon MJ
TitleReplacement of active-site cysteine-436 by serine converts cytochrome P450 2B4 into an NADPH oxidase with negligible monooxygenase activity.
[16]
CommentsX-ray crystallography
PubMed ID12767218
JournalBiochemistry
Year2003
Volume42
Pages6370-9
AuthorsWester MR, Johnson EF, Marques-Soares C, Dansette PM, Mansuy D, Stout CD
TitleStructure of a substrate complex of mammalian cytochrome P450 2C5 at 2.3 A resolution: evidence for multiple substrate binding modes.
Related PDB1n6b
Related UniProtKBP00179
[17]
CommentsX-ray crystallography
PubMed ID12899620
JournalBiochemistry
Year2003
Volume42
Pages9335-45
AuthorsWester MR, Johnson EF, Marques-Soares C, Dijols S, Dansette PM, Mansuy D, Stout CD
TitleStructure of mammalian cytochrome P450 2C5 complexed with diclofenac at 2.1 A resolution: evidence for an induced fit model of substrate binding.
Related PDB1nr6

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):

createdupdated
2004-10-202009-03-11


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