DB code: D00447

CATH domain 3.10.180.10 : 2,3-Dihydroxybiphenyl 1,2-Dioxygenase; domain 1
3.10.180.10 : 2,3-Dihydroxybiphenyl 1,2-Dioxygenase; domain 1 Catalytic domain
E.C. 1.13.11.27
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.10.180.10 : 2,3-Dihydroxybiphenyl 1,2-Dioxygenase; domain 1 D00446 D00448 S00540 S00185

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P80064 4-hydroxyphenylpyruvate dioxygenase
4HPPD
HPD
HPPDase
EC 1.13.11.27
PF00903 (Glyoxalase)
[Graphical View]
Q53586 4-hydroxyphenylpyruvate dioxygenase
4HPPD
HPD
HPPDase
EC 1.13.11.27
PF00903 (Glyoxalase)
PF12681 (Glyoxalase_2)
[Graphical View]
NP_826326.1 (Protein)
NC_003155.4 (DNA/RNA sequence)
O48604 4-hydroxyphenylpyruvate dioxygenase
EC 1.13.11.27
4-hydroxyphenylpyruvic acid oxidase
4HPPD
HPD
HPPDase
PF00903 (Glyoxalase)
[Graphical View]
P93836 4-hydroxyphenylpyruvate dioxygenase
EC 1.13.11.27
4-hydroxyphenylpyruvic acid oxidase
4HPPD
HPD
HPPDase
PF00903 (Glyoxalase)
[Graphical View]
NP_172144.2 (Protein)
NM_100536.3 (DNA/RNA sequence)

KEGG enzyme name
4-hydroxyphenylpyruvate dioxygenase
p-hydroxyphenylpyruvic hydroxylase
p-hydroxyphenylpyruvate hydroxylase
p-hydroxyphenylpyruvate oxidase
p-hydroxyphenylpyruvic oxidase
p-hydroxyphenylpyruvate dioxygenase
p-hydroxyphenylpyruvic acid hydroxylase
4-hydroxyphenylpyruvic acid dioxygenase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P80064 HPPD_PSEUJ 4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2). Homotetramer. Binds 1 iron ion per subunit.
Q53586 HPPD_STRAW 4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2). Homodimer. Binds 1 iron ion per subunit.
O48604 HPPD_HORVU 4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2). Cytoplasm (By similarity). Binds 1 iron ion per subunit (By similarity).
P93836 HPPD_ARATH 4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2). Homodimer. Cytoplasm. Binds 1 iron ion per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00360 Phenylalanine metabolism
MAP00350 Tyrosine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00023 C00007 C01179 C00011 C00544
E.C.
Compound Iron O2 3-(4-Hydroxyphenyl)pyruvate CO2 Homogentisate
Type heavy metal others aromatic ring (only carbon atom),carbohydrate,carboxyl group others aromatic ring (only carbon atom),carboxyl group
ChEBI 18248
82664
15379
26689
27140
15999
16526
44747
PubChem 23925
977
979
280
780
1cjxA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cjxB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cjxC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cjxD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1t47A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1t47B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1sp8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1sp8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1sp8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1sp8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1sp9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1sp9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1sqdA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1tfzA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cjxA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Intermediate-analogue:FE2-ACT
1cjxB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Intermediate-analogue:FE2-ACT
1cjxC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Intermediate-analogue:FE2-ACT
1cjxD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Intermediate-analogue:FE2-ACT
1t47A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Intermediate-analogue:FE2-NTD
1t47B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Intermediate-analogue:FE2-NTD
1sp8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Unbound
1sp8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Unbound
1sp8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Unbound
1sp8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Unbound
1sp9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Unbound
1sp9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Unbound
1sqdA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Unbound Unbound
1tfzA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Unbound Intermediate-analogue:_FE-869

Reference for Active-site residues
resource references E.C.
PDB;1cjx

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1cjxA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1cjxB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1cjxC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1cjxD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1t47A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1t47B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1sp8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1sp8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1sp8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1sp8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1sp9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1sp9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1sqdA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1tfzA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1cjxA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 161;HIS 240;GLU 322(Iron binding)
1cjxB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 161;HIS 240;GLU 322(Iron binding)
1cjxC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 161;HIS 240;GLU 322(Iron binding)
1cjxD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 161;HIS 240;GLU 322(Iron binding)
1t47A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 187;HIS 270;GLU 349(Iron binding)
1t47B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 187;HIS 270;GLU 349(Iron binding)
1sp8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 219;HIS 301;GLU 387(Iron binding)
1sp8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 219;HIS 301;GLU 387(Iron binding)
1sp8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 219;HIS 301;GLU 387(Iron binding)
1sp8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 219;HIS 301;GLU 387(Iron binding)
1sp9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226;HIS 308;GLU 394(Iron binding)
1sp9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226;HIS 308;GLU 394(Iron binding)
1sqdA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 205;HIS 287;GLU 373(Iron binding)
1tfzA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 205;HIS 287;GLU 373(Iron binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.4, Scheme I, p.3162-3164
[6]
Scheme 1, Scheme 2, p.1459-1460
[7]
p.979-981
[13]
Scheme 2, Scheme 3, Scheme 4, p.12334-12336
[15]
Scheme 2C, Scheme 3

References
[1]
Resource
Comments
Medline ID
PubMed ID 7274212
Journal Eur J Biochem
Year 1981
Volume 117
Pages 311-8
Authors Leinberger R, Hull WE, Simon H, Retey J
Title Steric course of the NIH shift in the enzymic formation of homogentisic acid.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 4027238
Journal Biochemistry
Year 1985
Volume 24
Pages 3158-65
Authors Pascal RA Jr, Oliver MA, Chen YC
Title Alternate substrates and inhibitors of bacterial 4-hydroxyphenylpyruvate dioxygenase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3017941
Journal J Biol Chem
Year 1986
Volume 261
Pages 11693-6
Authors Bradley FC, Lindstedt S, Lipscomb JD, Que L Jr, Roe AL, Rundgren M
Title 4-Hydroxyphenylpyruvate dioxygenase is an iron-tyrosinate protein.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1572351
Journal Eur J Biochem
Year 1992
Volume 205
Pages 459-66
Authors Ruetschi U, Odelhog B, Lindstedt S, Barros-Soderling J, Persson B, Jornvall H
Title Characterization of 4-hydroxyphenylpyruvate dioxygenase. Primary structure of the Pseudomonas enzyme.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7597701
Journal Toxicol Appl Pharmacol
Year 1995
Volume 133
Pages 12-9
Authors Ellis MK, Whitfield AC, Gowans LA, Auton TR, Provan WM, Lock EA, Smith LL
Title 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.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10465420
Journal Bioorg Med Chem
Year 1999
Volume 7
Pages 1459-65
Authors Ling TS, Shiu S, Yang DY
Title Design and synthesis of 3-fluoro-2-oxo-3-phenylpropionic acid derivatives as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase from pig liver.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10467142
Journal Structure Fold Des
Year 1999
Volume 7
Pages 977-88
Authors Serre L, Sailland A, Sy D, Boudec P, Rolland A, Pebay-Peyroula E, Cohen-Addad C
Title Crystal structure of Pseudomonas fluorescens 4-hydroxyphenylpyruvate dioxygenase: an enzyme involved in the tyrosine degradation pathway.
Related PDB 1cjx
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10853644
Journal Bioorg Med Chem Lett
Year 2000
Volume 10
Pages 843-5
Authors Lin YL, Wu CS, Lin SW, Yang DY
Title SAR studies of 2-o-substituted-benzoyl- and 2-alkanoyl-cyclohexane-1,3-diones as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 12067543
Journal Bioorg Med Chem Lett
Year 2002
Volume 12
Pages 1709-13
Authors Lin YL, Huang JL, Wu CS, Liu HG, Yang DY
Title Design, synthesis, and evaluation of postulated transient intermediate and substrate analogues as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 12014960
Journal J Med Chem
Year 2002
Volume 45
Pages 2222-8
Authors Wu CS, Huang JL, Sun YS, Yang DY
Title Mode of action of 4-hydroxyphenylpyruvate dioxygenase inhibition by triketone-type inhibitors.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 12031447
Journal Phytochemistry
Year 2002
Volume 60
Pages 281-8
Authors Meazza G, Scheffler BE, Tellez MR, Rimando AM, Romagni JG, Duke SO, Nanayakkara D, Khan IA, Abourashed EA, Dayan FE
Title The inhibitory activity of natural products on plant p-hydroxyphenylpyruvate dioxygenase.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12939152
Journal Biochemistry
Year 2003
Volume 42
Pages 10238-45
Authors Kavana M, Moran GR
Title Interaction of (4-hydroxyphenyl)pyruvate dioxygenase with the specific inhibitor 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 15379572
Journal Biochemistry
Year 2004
Volume 43
Pages 12331-42
Authors Borowski T, Bassan A, Siegbahn PE
Title 4-Hydroxyphenylpyruvate dioxygenase: a hybrid density functional study of the catalytic reaction mechanism.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 15157070
Journal Biochemistry
Year 2004
Volume 43
Pages 6370-7
Authors Brownlee JM, Johnson-Winters K, Harrison DH, Moran GR
Title Structure of the ferrous form of (4-hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis in complex with the therapeutic herbicide, NTBC.
Related PDB 1t47
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 14730970
Journal Biochemistry
Year 2004
Volume 43
Pages 663-74
Authors Gunsior M, Ravel J, Challis GL, Townsend CA
Title Engineering p-hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase and evidence for the proposed benzene oxide intermediate in homogentisate formation.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 15301540
Journal Biochemistry
Year 2004
Volume 43
Pages 10414-23
Authors Yang C, Pflugrath JW, Camper DL, Foster ML, Pernich DJ, Walsh TA
Title Structural basis for herbicidal inhibitor selectivity revealed by comparison of crystal structures of plant and mammalian 4-hydroxyphenylpyruvate dioxygenases.
Related PDB 1sqd 1tfz
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 15070344
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 4486-7
Authors Neidig ML, Kavana M, Moran GR, Solomon EI
Title 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.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 15084729
Journal Plant Physiol
Year 2004
Volume 134
Pages 1388-400
Authors Fritze IM, Linden L, Freigang J, Auerbach G, Huber R, Steinbacher S
Title The crystal structures of Zea mays and Arabidopsis 4-hydroxyphenylpyruvate dioxygenase.
Related PDB 1sp8 1sp9
Related UniProtKB

Comments

Created Updated
2004-10-28 2009-09-29