D00447
type: Enzyme
cath: 2,3-Dihydroxybiphenyl 1,2-Dioxygenase; domain 1
ec: https://purl.uniprot.org/enzyme/1.13.11.27
uniprot: P80064
uniprot: Q53586
uniprot: O48604
uniprot: P93836
kegg enzyme: 4-hydroxyphenylpyruvate dioxygenase
kegg enzyme: p-hydroxyphenylpyruvic hydroxylase
kegg enzyme: p-hydroxyphenylpyruvate hydroxylase
kegg enzyme: p-hydroxyphenylpyruvate oxidase
kegg enzyme: p-hydroxyphenylpyruvic oxidase
kegg enzyme: p-hydroxyphenylpyruvate dioxygenase
kegg enzyme: p-hydroxyphenylpyruvic acid hydroxylase
kegg enzyme: 4-hydroxyphenylpyruvic acid dioxygenase
kegg pathway: Tyrosine metabolism
kegg pathway: Phenylalanine metabolism
kegg cofactor: Iron
kegg substrate: O2
kegg substrate: 3-(4-Hydroxyphenyl)pyruvate
kegg product: CO2
kegg product: Homogentisate
pdb: 1cjxA01
pdb: 1cjxB01
pdb: 1cjxC01
pdb: 1cjxD01
pdb: 1t47A01
pdb: 1t47B01
pdb: 1sp8A01
pdb: 1sp8B01
pdb: 1sp8C01
pdb: 1sp8D01
pdb: 1sp9A01
pdb: 1sp9B01
pdb: 1sqdA01
pdb: 1tfzA01
pdb: 1cjxA02
pdb: 1cjxB02
pdb: 1cjxC02
pdb: 1cjxD02
pdb: 1t47A02
pdb: 1t47B02
pdb: 1sp8A02
pdb: 1sp8B02
pdb: 1sp8C02
pdb: 1sp8D02
pdb: 1sp9A02
pdb: 1sp9B02
pdb: 1sqdA02
pdb: 1tfzA02
pdb bound state: Unbound
  compound: O2
  pdb: 1cjxA01
pdb bound state: Unbound
  compound: O2
  pdb: 1cjxB01
pdb bound state: Unbound
  compound: O2
  pdb: 1cjxC01
pdb bound state: Unbound
  compound: O2
  pdb: 1cjxD01
pdb bound state: Unbound
  compound: O2
  pdb: 1t47A01
pdb bound state: Unbound
  compound: O2
  pdb: 1t47B01
pdb bound state: Unbound
  compound: O2
  pdb: 1sp8A01
pdb bound state: Unbound
  compound: O2
  pdb: 1sp8B01
pdb bound state: Unbound
  compound: O2
  pdb: 1sp8C01
pdb bound state: Unbound
  compound: O2
  pdb: 1sp8D01
pdb bound state: Unbound
  compound: O2
  pdb: 1sp9A01
active site residues resources: 1cjx
references: Steric course of the NIH shift in the enzymic formation of homogentisic acid.
references: Alternate substrates and inhibitors of bacterial 4-hydroxyphenylpyruvate dioxygenase.
references: 4-Hydroxyphenylpyruvate dioxygenase is an iron-tyrosinate protein.
references: Characterization of 4-hydroxyphenylpyruvate dioxygenase. Primary structure of the Pseudomonas enzyme.
references: Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dione.
references: Design and synthesis of 3-fluoro-2-oxo-3-phenylpropionic acid derivatives as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase from pig liver.
references: Crystal structure of Pseudomonas fluorescens 4-hydroxyphenylpyruvate dioxygenase: an enzyme involved in the tyrosine degradation pathway.
references: SAR studies of 2-o-substituted-benzoyl- and 2-alkanoyl-cyclohexane-1,3-diones as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
references: Design, synthesis, and evaluation of postulated transient intermediate and substrate analogues as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
references: Mode of action of 4-hydroxyphenylpyruvate dioxygenase inhibition by triketone-type inhibitors.
references: The inhibitory activity of natural products on plant p-hydroxyphenylpyruvate dioxygenase.
references: Interaction of (4-hydroxyphenyl)pyruvate dioxygenase with the specific inhibitor 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione.
references: 4-Hydroxyphenylpyruvate dioxygenase: a hybrid density functional study of the catalytic reaction mechanism.
references: Structure of the ferrous form of (4-hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis in complex with the therapeutic herbicide, NTBC.
references: Engineering p-hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase and evidence for the proposed benzene oxide intermediate in homogentisate formation.
references: Structural basis for herbicidal inhibitor selectivity revealed by comparison of crystal structures of plant and mammalian 4-hydroxyphenylpyruvate dioxygenases.
references: CD and MCD studies of the non-heme ferrous active site in (4-hydroxyphenyl)pyruvate dioxygenase: correlation between oxygen activation in the extradiol and alpha-KG-dependent dioxygenases.
references: The crystal structures of Zea mays and Arabidopsis 4-hydroxyphenylpyruvate dioxygenase.

2,3-Dihydroxybiphenyl 1,2-Dioxygenase; domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.10.180.10
catalytic domain: index.html

Tyrosine metabolism
type: KeggPathway
references: KEGG:MAP00350

Phenylalanine metabolism
type: KeggPathway
references: KEGG:MAP00360

Iron
type: KeggCofactor
references: KEGG:C00023
compound type: heavy metal
references: CHEBI:18248
references: CHEBI:82664
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

O2
type: KeggSubstrate
references: KEGG:C00007
compound type: others
references: CHEBI:15379
references: CHEBI:26689
references: CHEBI:27140
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

3-(4-Hydroxyphenyl)pyruvate
type: KeggSubstrate
references: KEGG:C01179
compound type: aromatic ring (only carbon atom)
compound type: carbohydrate
compound type: carboxyl group
references: CHEBI:15999
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

CO2
type: KeggProduct
references: KEGG:C00011
compound type: others
references: CHEBI:16526
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Homogentisate
type: KeggProduct
references: KEGG:C00544
compound type: aromatic ring (only carbon atom)
compound type: carboxyl group
references: CHEBI:44747
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1cjxA02
type: Pdb
references: 1cjx
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cjx
cofactor binding residue: HIS 161;HIS 240;GLU 322(Iron binding)

1cjxB02
type: Pdb
references: 1cjx
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cjx
cofactor binding residue: HIS 161;HIS 240;GLU 322(Iron binding)

1cjxC02
type: Pdb
references: 1cjx
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cjx
cofactor binding residue: HIS 161;HIS 240;GLU 322(Iron binding)

1cjxD02
type: Pdb
references: 1cjx
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1cjx
cofactor binding residue: HIS 161;HIS 240;GLU 322(Iron binding)

1t47A02
type: Pdb
references: 1t47
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1t47
cofactor binding residue: HIS 187;HIS 270;GLU 349(Iron binding)

1t47B02
type: Pdb
references: 1t47
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1t47
cofactor binding residue: HIS 187;HIS 270;GLU 349(Iron binding)

1sp8A02
type: Pdb
references: 1sp8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1sp8
cofactor binding residue: HIS 219;HIS 301;GLU 387(Iron binding)

1sp8B02
type: Pdb
references: 1sp8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1sp8
cofactor binding residue: HIS 219;HIS 301;GLU 387(Iron binding)

1sp8C02
type: Pdb
references: 1sp8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1sp8
cofactor binding residue: HIS 219;HIS 301;GLU 387(Iron binding)

1sp8D02
type: Pdb
references: 1sp8
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1sp8
cofactor binding residue: HIS 219;HIS 301;GLU 387(Iron binding)

1sp9A02
type: Pdb
references: 1sp9
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1sp9
cofactor binding residue: HIS 226;HIS 308;GLU 394(Iron binding)

1sp9B02
type: Pdb
references: 1sp9
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1sp9
cofactor binding residue: HIS 226;HIS 308;GLU 394(Iron binding)

1sqdA02
type: Pdb
references: 1sqd
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1sqd
cofactor binding residue: HIS 205;HIS 287;GLU 373(Iron binding)

1tfzA02
type: Pdb
references: 1tfz
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1tfz
cofactor binding residue: HIS 205;HIS 287;GLU 373(Iron binding)

Steric course of the NIH shift in the enzymic formation of homogentisic acid.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7274212
journal: Eur J Biochem
volume: 117
pages: 311-8
published year: 1981
authors:
  item: Leinberger R
  item: Hull WE
  item: Simon H
  item: Retey J

Alternate substrates and inhibitors of bacterial 4-hydroxyphenylpyruvate dioxygenase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/4027238
journal: Biochemistry
volume: 24
pages: 3158-65
published year: 1985
authors:
  item: Pascal RA Jr
  item: Oliver MA
  item: Chen YC

4-Hydroxyphenylpyruvate dioxygenase is an iron-tyrosinate protein.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/3017941
journal: J Biol Chem
volume: 261
pages: 11693-6
published year: 1986
authors:
  item: Bradley FC
  item: Lindstedt S
  item: Lipscomb JD
  item: Que L Jr
  item: Roe AL
  item: Rundgren M

Characterization of 4-hydroxyphenylpyruvate dioxygenase. Primary structure of the Pseudomonas enzyme.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1572351
journal: Eur J Biochem
volume: 205
pages: 459-66
published year: 1992
authors:
  item: Ruetschi U
  item: Odelhog B
  item: Lindstedt S
  item: Barros-Soderling J
  item: Persson B
  item: Jornvall H

Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dione.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7597701
journal: Toxicol Appl Pharmacol
volume: 133
pages: 12-9
published year: 1995
authors:
  item: Ellis MK
  item: Whitfield AC
  item: Gowans LA
  item: Auton TR
  item: Provan WM
  item: Lock EA
  item: Smith LL

Design and synthesis of 3-fluoro-2-oxo-3-phenylpropionic acid derivatives as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase from pig liver.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10465420
journal: Bioorg Med Chem
volume: 7
pages: 1459-65
published year: 1999
authors:
  item: Ling TS
  item: Shiu S
  item: Yang DY

Crystal structure of Pseudomonas fluorescens 4-hydroxyphenylpyruvate dioxygenase: an enzyme involved in the tyrosine degradation pathway.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/10467142
journal: Structure Fold Des
volume: 7
pages: 977-88
published year: 1999
authors:
  item: Serre L
  item: Sailland A
  item: Sy D
  item: Boudec P
  item: Rolland A
  item: Pebay-Peyroula E
  item: Cohen-Addad C
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

SAR studies of 2-o-substituted-benzoyl- and 2-alkanoyl-cyclohexane-1,3-diones as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10853644
journal: Bioorg Med Chem Lett
volume: 10
pages: 843-5
published year: 2000
authors:
  item: Lin YL
  item: Wu CS
  item: Lin SW
  item: Yang DY

Design, synthesis, and evaluation of postulated transient intermediate and substrate analogues as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12067543
journal: Bioorg Med Chem Lett
volume: 12
pages: 1709-13
published year: 2002
authors:
  item: Lin YL
  item: Huang JL
  item: Wu CS
  item: Liu HG
  item: Yang DY

Mode of action of 4-hydroxyphenylpyruvate dioxygenase inhibition by triketone-type inhibitors.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12014960
journal: J Med Chem
volume: 45
pages: 2222-8
published year: 2002
authors:
  item: Wu CS
  item: Huang JL
  item: Sun YS
  item: Yang DY

The inhibitory activity of natural products on plant p-hydroxyphenylpyruvate dioxygenase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12031447
journal: Phytochemistry
volume: 60
pages: 281-8
published year: 2002
authors:
  item: Meazza G
  item: Scheffler BE
  item: Tellez MR
  item: Rimando AM
  item: Romagni JG
  item: Duke SO
  item: Nanayakkara D
  item: Khan IA
  item: Abourashed EA
  item: Dayan FE

Interaction of (4-hydroxyphenyl)pyruvate dioxygenase with the specific inhibitor 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12939152
journal: Biochemistry
volume: 42
pages: 10238-45
published year: 2003
authors:
  item: Kavana M
  item: Moran GR

4-Hydroxyphenylpyruvate dioxygenase: a hybrid density functional study of the catalytic reaction mechanism.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15379572
journal: Biochemistry
volume: 43
pages: 12331-42
published year: 2004
authors:
  item: Borowski T
  item: Bassan A
  item: Siegbahn PE

Structure of the ferrous form of (4-hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis in complex with the therapeutic herbicide, NTBC.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15157070
journal: Biochemistry
volume: 43
pages: 6370-7
published year: 2004
authors:
  item: Brownlee JM
  item: Johnson-Winters K
  item: Harrison DH
  item: Moran GR
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Engineering p-hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase and evidence for the proposed benzene oxide intermediate in homogentisate formation.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/14730970
journal: Biochemistry
volume: 43
pages: 663-74
published year: 2004
authors:
  item: Gunsior M
  item: Ravel J
  item: Challis GL
  item: Townsend CA

Structural basis for herbicidal inhibitor selectivity revealed by comparison of crystal structures of plant and mammalian 4-hydroxyphenylpyruvate dioxygenases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15301540
journal: Biochemistry
volume: 43
pages: 10414-23
published year: 2004
authors:
  item: Yang C
  item: Pflugrath JW
  item: Camper DL
  item: Foster ML
  item: Pernich DJ
  item: Walsh TA
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

CD and MCD studies of the non-heme ferrous active site in (4-hydroxyphenyl)pyruvate dioxygenase: correlation between oxygen activation in the extradiol and alpha-KG-dependent dioxygenases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15070344
journal: J Am Chem Soc
volume: 126
pages: 4486-7
published year: 2004
authors:
  item: Neidig ML
  item: Kavana M
  item: Moran GR
  item: Solomon EI

The crystal structures of Zea mays and Arabidopsis 4-hydroxyphenylpyruvate dioxygenase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15084729
journal: Plant Physiol
volume: 134
pages: 1388-400
published year: 2004
authors:
  item: Fritze IM
  item: Linden L
  item: Freigang J
  item: Auerbach G
  item: Huber R
  item: Steinbacher S
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

IntermediateAnalogue
pdb: 1cjxA02
ligand het code: FE2-ACT

IntermediateAnalogue
pdb: 1cjxB02
ligand het code: FE2-ACT

IntermediateAnalogue
pdb: 1cjxC02
ligand het code: FE2-ACT

IntermediateAnalogue
pdb: 1cjxD02
ligand het code: FE2-ACT

IntermediateAnalogue
pdb: 1t47A02
ligand het code: FE2-NTD

IntermediateAnalogue
pdb: 1t47B02
ligand het code: FE2-NTD

IntermediateAnalogue
pdb: 1tfzA02
ligand het code: _FE-869

ReferenceForCatalyticMechanism
reference index: 2
reference section: Fig.4, Scheme I, p.3162-3164

ReferenceForCatalyticMechanism
reference index: 6
reference section: Scheme 1, Scheme 2, p.1459-1460

ReferenceForCatalyticMechanism
reference index: 7
reference section: p.979-981

ReferenceForCatalyticMechanism
reference index: 13
reference section: Scheme 2, Scheme 3, Scheme 4, p.12334-12336

ReferenceForCatalyticMechanism
reference index: 15
reference section: Scheme 2C, Scheme 3