DB code: M00179

CATH domain 3.40.462.10 : Vanillyl-alcohol Oxidase; Chain A, domain 3 Catalytic domain
3.30.43.10 : Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase; domain 2
3.30.465.20 : Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase; domain 3 Catalytic domain
1.10.45.10 : Vanillyl-alcohol Oxidase; Chain A, domain 4 Catalytic domain
1.10.760.10 : Cytochrome Bc1 Complex; Chain D, domain 2 Catalytic domain
E.C. 1.17.99.1
CSA 1dii
M-CSA 1dii
MACiE M0141

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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P09787 4-cresol dehydrogenase [hydroxylating] cytochrome c subunit
Flavocytochrome c
P-cresol methylhydroxylase cytochrome subunit
[Graphical View]
P09788 4-cresol dehydrogenase [hydroxylating] flavoprotein subunit
EC 1.17.99.1
P-cresol methylhydroxylase
PCMH
PF02913 (FAD-oxidase_C)
PF01565 (FAD_binding_4)
[Graphical View]

KEGG enzyme name
4-cresol dehydrogenase (hydroxylating)
p-cresol-(acceptor) oxidoreductase (hydroxylating)
p-cresol methylhydroxylase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P09788 DH4C_PSEPU 4-cresol + acceptor + H(2)O = 4- hydroxybenzaldehyde + reduced acceptor. Tetramer of two cytochrome subunits and two flavoprotein subunits. Binds 1 FAD covalently per subunit.
P09787 CY4C_PSEPU Tetramer of two cytochrome subunits and two flavoprotein subunits.

KEGG Pathways
Map code Pathways E.C.
MAP00622 Toluene and xylene degradation

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00016 C00524 C01468 C00028 C00001 C00633 C00030
E.C.
Compound FAD Cytochrome c 4-Cresol Acceptor H2O 4-Hydroxybenzaldehyde Reduced acceptor quinone-methide intermediate 4-hydroxybenzyl alcohol
Type amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotide amide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide group aromatic ring (only carbon atom) others H2O aromatic ring (only carbon atom),carbohydrate others
ChEBI 16238
17847
15377
17597
PubChem 643975
2879
22247451
962
126
1diiA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diiB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diqA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:PCR Unbound Unbound Unbound
1diqB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:PCR Unbound Unbound Unbound
1wveA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1wveB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1wvfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diiA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound
1diiB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound
1diqA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound
1diqB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound
1wveA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound
1wveB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound
1wvfA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Unbound Unbound Unbound Unbound Unbound
1diiA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diiB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diqA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diqB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1wveA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1wveB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1wvfA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diiA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diiB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diqA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diqB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1wveA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1wveB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1wvfA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1diiC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:HEM Unbound Unbound Unbound Unbound
1diiD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:HEM Unbound Unbound Unbound Unbound
1diqC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:HEM Unbound Unbound Unbound Unbound
1diqD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:HEM Unbound Unbound Unbound Unbound
1wveC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:HEM Unbound Unbound Unbound Unbound
1wveD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:HEM Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P09787, P09788 & literature [8]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1diiA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 95
1diiB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 95
1diqA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 95
1diqB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 95
1wveA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 95
1wveB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 95
1wvfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 95
1diiA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1diiB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1diqA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1diqB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1wveA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1wveB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1wvfA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1diiA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 380;GLU 427;HIS 436;TYR 473 TYR 384(FAD binding)
1diiB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 380;GLU 427;HIS 436;TYR 473 TYR 384(FAD binding)
1diqA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 380;GLU 427;HIS 436;TYR 473 TYR 384(FAD binding)
1diqB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 380;GLU 427;HIS 436;TYR 473 TYR 384(FAD binding)
1wveA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 380;GLU 427;HIS 436;TYR 473 TYR 384(FAD binding)
1wveB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 380;GLU 427;HIS 436;TYR 473 TYR 384(FAD binding)
1wvfA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 380;GLU 427;HIS 436;TYR 473 TYR 384(FAD binding)
1diiA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 474
1diiB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 474
1diqA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 474
1diqB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 474
1wveA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 474
1wveB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 474
1wvfA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 474
1diiC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 619;MET 650(Heme binding) ALA 649
1diiD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 619;MET 650(Heme binding) ALA 649
1diqC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 619;MET 650(Heme binding) ALA 649
1diqD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 619;MET 650(Heme binding) ALA 649
1wveC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 619;MET 650(Heme binding) ALA 649
1wveD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 619;MET 650(Heme binding) ALA 649

References for Catalytic Mechanism
References Sections No. 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.2963 3

References
[1]
Resource
Comments
Medline ID
PubMed ID 4020868
Journal J Mol Biol
Year 1985
Volume 183
Pages 517-8
Authors Shamala N, Lim LW, Mathews FS, McIntire W, Singer TP, Hopper DJ
Title Preliminary X-ray study of p-cresol methylhydroxylase (flavocytochrome c) from Pseudomonas putida N.C.I.B. 9869.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3460064
Journal Proc Natl Acad Sci U S A
Year 1986
Volume 83
Pages 4646-9
Authors Bruice TC, Zipplies MF, Lee WA
Title The pH dependence of the mechanism of reaction of hydrogen peroxide with a nonaggregating, non-mu-oxo dimer-forming iron (III) porphyrin in water.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS)
Medline ID 91105087
PubMed ID 1846290
Journal Biochemistry
Year 1991
Volume 30
Pages 238-47
Authors Mathews FS, Chen ZW, Bellamy HD, McIntire WS
Title Three-dimensional structure of p-cresol methylhydroxylase (flavocytochrome c) from Pseudomonas putida at 3.0-A resolution.
Related PDB
Related UniProtKB P09787 P09788
[4]
Resource
Comments
Medline ID
PubMed ID 1946360
Journal Proc Natl Acad Sci U S A
Year 1991
Volume 88
Pages 9463-7
Authors McLendon GL, Bagby S, Charman JA, Driscoll PC, McIntire WS, Mathews FS, Hill HA
Title Subunit interactions change the heme active-site geometry in p-cresol methylhydroxylase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8537385
Journal J Biol Chem
Year 1995
Volume 270
Pages 31202-9
Authors Kim J, Fuller JH, Kuusk V, Cunane L, Chen ZW, Mathews FS, McIntire WS
Title The cytochrome subunit is necessary for covalent FAD attachment to the flavoprotein subunit of p-cresol methylhydroxylase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9514256
Journal Protein Sci
Year 1998
Volume 7
Pages 7-20
Authors Mewies M, McIntire WS, Scrutton NS
Title Covalent attachment of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) to enzymes: the current state of affairs.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10600124
Journal Biochemistry
Year 1999
Volume 38
Pages 16620-8
Authors Engst S, Kuusk V, Efimov I, Cronin CN, McIntire WS
Title Properties of p-cresol methylhydroxylase flavoprotein overproduced by Escherichia coli.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)
Medline ID 20090938
PubMed ID 10623531
Journal J Mol Biol
Year 2000
Volume 295
Pages 357-74
Authors Cunane LM, Chen ZW, Shamala N, Mathews FS, Cronin CN, McIntire WS
Title Structures of the flavocytochrome p-cresol methylhydroxylase and its enzyme-substrate complex: gated substrate entry and proton relays support the proposed catalytic mechanism.
Related PDB 1dii 1diq
Related UniProtKB P09787 P09788
[9]
Resource
Comments
Medline ID
PubMed ID 11192725
Journal Subcell Biochem
Year 2000
Volume 35
Pages 29-72
Authors Mathews FS, Cunane L, Durley RC
Title Flavin electron transfer proteins.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11329284
Journal Biochemistry
Year 2001
Volume 40
Pages 2155-66
Authors Efimov I, Cronin CN, McIntire WS
Title Effects of noncovalent and covalent FAD binding on the redox and catalytic properties of p-cresol methylhydroxylase.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11514662
Journal Protein Sci
Year 2001
Volume 10
Pages 1712-28
Authors Dym O, Eisenberg D
Title Sequence-structure analysis of FAD-containing proteins.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12057198
Journal Structure (Camb)
Year 2002
Volume 10
Pages 837-49
Authors Chen ZW, Matsushita K, Yamashita T, Fujii TA, Toyama H, Adachi O, Bellamy HD, Mathews FS
Title Structure at 1.9 A resolution of a quinohemoprotein alcohol dehydrogenase from Pseudomonas putida HK5.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 15147198
Journal Biochemistry
Year 2004
Volume 43
Pages 6138-48
Authors Efimov I, Cronin CN, Bergmann DJ, Kuusk V, McIntire WS
Title Insight into covalent flavinylation and catalysis from redox, spectral, and kinetic analyses of the R474K mutant of the flavoprotein subunit of p-cresol methylhydroxylase.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 15301551
Journal Biochemistry
Year 2004
Volume 43
Pages 10532-46
Authors Efimov I, McIntire WS
Title A study of the spectral and redox properties and covalent flavinylation of the flavoprotein component of p-cresol methylhydroxylase reconstituted with FAD analogues.
Related PDB
Related UniProtKB
[15]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12614613
Journal J Mol Biol
Year 2003
Volume 327
Pages 129-44
Authors Nichols CE, Ren J, Lamb HK, Hawkins AR, Stammers DK
Title Ligand-induced conformational changes and a mechanism for domain closure in Aspergillus nidulans dehydroquinate synthase.
Related PDB 1wve 1wvf
Related UniProtKB

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".

Created Updated
2005-05-19 2009-02-26