EzCatDB: M00179
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DB codeM00179
CATH domainDomain 13.40.462.10 : Vanillyl-alcohol Oxidase; Chain A, domain 3Catalytic domain
Domain 23.30.43.10 : Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase; domain 2
Domain 33.30.465.20 : Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase; domain 3Catalytic domain
Domain 41.10.45.10 : Vanillyl-alcohol Oxidase; Chain A, domain 4Catalytic domain
Domain 51.10.760.10 : Cytochrome Bc1 Complex; Chain D, domain 2Catalytic domain
E.C.1.17.99.1
CSA1dii
MACiEM0141

CATH domainRelated DB codes (homologues)
1.10.45.10 : Vanillyl-alcohol Oxidase; Chain A, domain 4M00004
1.10.760.10 : Cytochrome Bc1 Complex; Chain D, domain 2D00055,D00498
3.30.43.10 : Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase; domain 2M00001,M00004,M00039,T00003
3.30.465.20 : Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase; domain 3M00001,M00004
3.40.462.10 : Vanillyl-alcohol Oxidase; Chain A, domain 3M00004

Enzyme Name
UniProtKBKEGG

P09787P09788
Protein name4-cresol dehydrogenase [hydroxylating] cytochrome c subunit4-cresol dehydrogenase [hydroxylating] flavoprotein subunit4-cresol dehydrogenase (hydroxylating)
p-cresol-(acceptor) oxidoreductase (hydroxylating)
p-cresol methylhydroxylase
SynonymsFlavocytochrome c
P-cresol methylhydroxylase cytochrome subunit
EC 1.17.99.1
P-cresol methylhydroxylase
PCMH
Pfam
PF02913 (FAD-oxidase_C)
PF01565 (FAD_binding_4)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00622Toluene and xylene degradation

UniProtKB:Accession NumberP09787P09788
Entry nameCY4C_PSEPUDH4C_PSEPU
Activity
4-cresol + acceptor + H(2)O = 4- hydroxybenzaldehyde + reduced acceptor.
SubunitTetramer of two cytochrome subunits and two flavoprotein subunits.Tetramer of two cytochrome subunits and two flavoprotein subunits.
Subcellular location

Cofactor
Binds 1 FAD covalently per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00016C00524C01468C00028C00001C00633C00030

CompoundFADCytochrome c4-CresolAcceptorH2O4-HydroxybenzaldehydeReduced acceptorquinone-methide intermediate4-hydroxybenzyl alcohol
Typeamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotideamide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide grouparomatic ring (only carbon atom)othersH2Oaromatic ring (only carbon atom),carbohydrateothers

ChEBI16238

17847

15377
17597



PubChem643975

2879

962
22247451
126



                 
1diiA01UnboundUnboundUnboundUnbound UnboundUnbound  
1diiB01UnboundUnboundUnboundUnbound UnboundUnbound  
1diqA01UnboundUnboundBound:PCRUnbound UnboundUnbound  
1diqB01UnboundUnboundBound:PCRUnbound UnboundUnbound  
1wveA01UnboundUnboundUnboundUnbound UnboundUnbound  
1wveB01UnboundUnboundUnboundUnbound UnboundUnbound  
1wvfA01UnboundUnboundUnboundUnbound UnboundUnbound  
1diiA02Bound:FADUnboundUnboundUnbound UnboundUnbound  
1diiB02Bound:FADUnboundUnboundUnbound UnboundUnbound  
1diqA02Bound:FADUnboundUnboundUnbound UnboundUnbound  
1diqB02Bound:FADUnboundUnboundUnbound UnboundUnbound  
1wveA02Bound:FADUnboundUnboundUnbound UnboundUnbound  
1wveB02Bound:FADUnboundUnboundUnbound UnboundUnbound  
1wvfA02Bound:FADUnboundUnboundUnbound UnboundUnbound  
1diiA03UnboundUnboundUnboundUnbound UnboundUnbound  
1diiB03UnboundUnboundUnboundUnbound UnboundUnbound  
1diqA03UnboundUnboundUnboundUnbound UnboundUnbound  
1diqB03UnboundUnboundUnboundUnbound UnboundUnbound  
1wveA03UnboundUnboundUnboundUnbound UnboundUnbound  
1wveB03UnboundUnboundUnboundUnbound UnboundUnbound  
1wvfA03UnboundUnboundUnboundUnbound UnboundUnbound  
1diiA04UnboundUnboundUnboundUnbound UnboundUnbound  
1diiB04UnboundUnboundUnboundUnbound UnboundUnbound  
1diqA04UnboundUnboundUnboundUnbound UnboundUnbound  
1diqB04UnboundUnboundUnboundUnbound UnboundUnbound  
1wveA04UnboundUnboundUnboundUnbound UnboundUnbound  
1wveB04UnboundUnboundUnboundUnbound UnboundUnbound  
1wvfA04UnboundUnboundUnboundUnbound UnboundUnbound  
1diiCUnboundAnalogue:HEMUnboundUnbound UnboundUnbound  
1diiDUnboundAnalogue:HEMUnboundUnbound UnboundUnbound  
1diqCUnboundAnalogue:HEMUnboundUnbound UnboundUnbound  
1diqDUnboundAnalogue:HEMUnboundUnbound UnboundUnbound  
1wveCUnboundAnalogue:HEMUnboundUnbound UnboundUnbound  
1wveDUnboundAnalogue:HEMUnboundUnbound UnboundUnbound  

Active-site residues
resource
Swiss-prot;P09787, P09788 & literature [8]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysis
           
1diiA01TYR 95
 
 
1diiB01TYR 95
 
 
1diqA01TYR 95
 
 
1diqB01TYR 95
 
 
1wveA01TYR 95
 
 
1wveB01TYR 95
 
 
1wvfA01TYR 95
 
 
1diiA02 
 
 
1diiB02 
 
 
1diqA02 
 
 
1diqB02 
 
 
1wveA02 
 
 
1wveB02 
 
 
1wvfA02 
 
 
1diiA03GLU 380;GLU 427;HIS 436;TYR 473
TYR 384(FAD binding)
 
1diiB03GLU 380;GLU 427;HIS 436;TYR 473
TYR 384(FAD binding)
 
1diqA03GLU 380;GLU 427;HIS 436;TYR 473
TYR 384(FAD binding)
 
1diqB03GLU 380;GLU 427;HIS 436;TYR 473
TYR 384(FAD binding)
 
1wveA03GLU 380;GLU 427;HIS 436;TYR 473
TYR 384(FAD binding)
 
1wveB03GLU 380;GLU 427;HIS 436;TYR 473
TYR 384(FAD binding)
 
1wvfA03GLU 380;GLU 427;HIS 436;TYR 473
TYR 384(FAD binding)
 
1diiA04ARG 474
 
 
1diiB04ARG 474
 
 
1diqA04ARG 474
 
 
1diqB04ARG 474
 
 
1wveA04ARG 474
 
 
1wveB04ARG 474
 
 
1wvfA04ARG 474
 
 
1diiC 
HIS 619;MET 650(Heme binding)
ALA 649
1diiD 
HIS 619;MET 650(Heme binding)
ALA 649
1diqC 
HIS 619;MET 650(Heme binding)
ALA 649
1diqD 
HIS 619;MET 650(Heme binding)
ALA 649
1wveC 
HIS 619;MET 650(Heme binding)
ALA 649
1wveD 
HIS 619;MET 650(Heme binding)
ALA 649

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]Fig.5, p.31207
[8]Fig.1, Fig.12, p.367-371
[14]p.10543-10545
[15]Fig.1, p.29633

references
[1]
PubMed ID4020868
JournalJ Mol Biol
Year1985
Volume183
Pages517-8
AuthorsShamala N, Lim LW, Mathews FS, McIntire W, Singer TP, Hopper DJ
TitlePreliminary X-ray study of p-cresol methylhydroxylase (flavocytochrome c) from Pseudomonas putida N.C.I.B. 9869.
[2]
PubMed ID3460064
JournalProc Natl Acad Sci U S A
Year1986
Volume83
Pages4646-9
AuthorsBruice TC, Zipplies MF, Lee WA
TitleThe pH dependence of the mechanism of reaction of hydrogen peroxide with a nonaggregating, non-mu-oxo dimer-forming iron (III) porphyrin in water.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS)
Medline ID91105087
PubMed ID1846290
JournalBiochemistry
Year1991
Volume30
Pages238-47
AuthorsMathews FS, Chen ZW, Bellamy HD, McIntire WS
TitleThree-dimensional structure of p-cresol methylhydroxylase (flavocytochrome c) from Pseudomonas putida at 3.0-A resolution.
Related UniProtKBP09787,P09788
[4]
PubMed ID1946360
JournalProc Natl Acad Sci U S A
Year1991
Volume88
Pages9463-7
AuthorsMcLendon GL, Bagby S, Charman JA, Driscoll PC, McIntire WS, Mathews FS, Hill HA
TitleSubunit interactions change the heme active-site geometry in p-cresol methylhydroxylase.
[5]
PubMed ID8537385
JournalJ Biol Chem
Year1995
Volume270
Pages31202-9
AuthorsKim J, Fuller JH, Kuusk V, Cunane L, Chen ZW, Mathews FS, McIntire WS
TitleThe cytochrome subunit is necessary for covalent FAD attachment to the flavoprotein subunit of p-cresol methylhydroxylase.
[6]
PubMed ID9514256
JournalProtein Sci
Year1998
Volume7
Pages7-20
AuthorsMewies M, McIntire WS, Scrutton NS
TitleCovalent attachment of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) to enzymes: the current state of affairs.
[7]
PubMed ID10600124
JournalBiochemistry
Year1999
Volume38
Pages16620-8
AuthorsEngst S, Kuusk V, Efimov I, Cronin CN, McIntire WS
TitleProperties of p-cresol methylhydroxylase flavoprotein overproduced by Escherichia coli.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)
Medline ID20090938
PubMed ID10623531
JournalJ Mol Biol
Year2000
Volume295
Pages357-74
AuthorsCunane LM, Chen ZW, Shamala N, Mathews FS, Cronin CN, McIntire WS
TitleStructures of the flavocytochrome p-cresol methylhydroxylase and its enzyme-substrate complex: gated substrate entry and proton relays support the proposed catalytic mechanism.
Related PDB1dii,1diq
Related UniProtKBP09787,P09788
[9]
PubMed ID11192725
JournalSubcell Biochem
Year2000
Volume35
Pages29-72
AuthorsMathews FS, Cunane L, Durley RC
TitleFlavin electron transfer proteins.
[10]
PubMed ID11329284
JournalBiochemistry
Year2001
Volume40
Pages2155-66
AuthorsEfimov I, Cronin CN, McIntire WS
TitleEffects of noncovalent and covalent FAD binding on the redox and catalytic properties of p-cresol methylhydroxylase.
[11]
PubMed ID11514662
JournalProtein Sci
Year2001
Volume10
Pages1712-28
AuthorsDym O, Eisenberg D
TitleSequence-structure analysis of FAD-containing proteins.
[12]
PubMed ID12057198
JournalStructure (Camb)
Year2002
Volume10
Pages837-49
AuthorsChen ZW, Matsushita K, Yamashita T, Fujii TA, Toyama H, Adachi O, Bellamy HD, Mathews FS
TitleStructure at 1.9 A resolution of a quinohemoprotein alcohol dehydrogenase from Pseudomonas putida HK5.
[13]
PubMed ID15147198
JournalBiochemistry
Year2004
Volume43
Pages6138-48
AuthorsEfimov I, Cronin CN, Bergmann DJ, Kuusk V, McIntire WS
TitleInsight into covalent flavinylation and catalysis from redox, spectral, and kinetic analyses of the R474K mutant of the flavoprotein subunit of p-cresol methylhydroxylase.
[14]
PubMed ID15301551
JournalBiochemistry
Year2004
Volume43
Pages10532-46
AuthorsEfimov I, McIntire WS
TitleA study of the spectral and redox properties and covalent flavinylation of the flavoprotein component of p-cresol methylhydroxylase reconstituted with FAD analogues.
[15]
CommentsX-ray crystallography
PubMed ID12614613
JournalJ Mol Biol
Year2003
Volume327
Pages129-44
AuthorsNichols CE, Ren J, Lamb HK, Hawkins AR, Stammers DK
TitleLigand-induced conformational changes and a mechanism for domain closure in Aspergillus nidulans dehydroquinate synthase.
Related PDB1wve,1wvf

comments
This enzyme is composed of flavoprotein subunit and cytochrome c subunit with a heme group.
According to the literature [8], [15], this enzyme catalyzes the following reactions:
(A) Hydride transfer from substrate, p-cresol, to flavin of FAD, forming a quinone-methide intermediate (transfer of two electrons and two protons):
(B) Electron transfer from the flavin of FAD to the heme iron of the cytochrome c subunit (2 x one electron transfer):
(C) Addition of water to the methide carbon of the quinone-methide intermediate, forming a 4-hydroxybenzyl alcohol (Hydroxylation):
(D) Hydride transfer from the intermediate, 4-hydroxybenzyl alcohol, to flavin of FAD, forming a product, p-hydroxybenzaldehyde (transfer of two electrons and two protons):
(E) Electron transfer from the flavin of FAD to the heme iron of the cytochrome c subunit (2 x one electron transfer):
# Electrons, transferred to the heme group, might be passed to the other substrate, "acceptor".

createdupdated
2005-05-192009-02-26


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