EzCatDB: D00447
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DB codeD00447
CATH domainDomain 13.10.180.10 : 2,3-Dihydroxybiphenyl 1,2-Dioxygenase; domain 1
Domain 23.10.180.10 : 2,3-Dihydroxybiphenyl 1,2-Dioxygenase; domain 1Catalytic domain
E.C.1.13.11.27

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

Enzyme Name
UniProtKBKEGG

P80064Q53586O48604P93836
Protein name4-hydroxyphenylpyruvate dioxygenase4-hydroxyphenylpyruvate dioxygenase4-hydroxyphenylpyruvate dioxygenase4-hydroxyphenylpyruvate dioxygenase4-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
SynonymsHPPDase
4HPPD
HPD
EC 1.13.11.27
HPPDase
4HPPD
HPD
EC 1.13.11.27
EC 1.13.11.27
4-hydroxyphenylpyruvic acid oxidase
HPPDase
4HPPD
HPD
EC 1.13.11.27
4-hydroxyphenylpyruvic acid oxidase
HPPDase
4HPPD
HPD
RefSeq
NP_826326.1 (Protein)
NC_003155.4 (DNA/RNA sequence)

NP_172144.2 (Protein)
NM_100536.3 (DNA/RNA sequence)
PfamPF00903 (Glyoxalase)
[Graphical view]
PF00903 (Glyoxalase)
PF12681 (Glyoxalase_2)
[Graphical view]
PF00903 (Glyoxalase)
[Graphical view]
PF00903 (Glyoxalase)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00350Tyrosine metabolism
MAP00360Phenylalanine metabolism

UniProtKB:Accession NumberP80064Q53586O48604P93836
Entry nameHPPD_PSEUJHPPD_STRAWHPPD_HORVUHPPD_ARATH
Activity4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2).4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2).4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2).4-hydroxyphenylpyruvate + O(2) = homogentisate + CO(2).
SubunitHomotetramer.Homodimer.
Homodimer.
Subcellular location

Cytoplasm (By similarity).Cytoplasm.
CofactorBinds 1 iron ion per subunit.Binds 1 iron ion per subunit.Binds 1 iron ion per subunit (By similarity).Binds 1 iron ion per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00023C00007C01179C00011C00544
CompoundIronO23-(4-Hydroxyphenyl)pyruvateCO2Homogentisate
Typeheavy metalothersaromatic ring (only carbon atom),carbohydrate,carboxyl groupothersaromatic ring (only carbon atom),carboxyl group
ChEBI18248
82664
27140
26689
15379
15999
16526
44747

PubChem23925
977
979
280
780

              
1cjxA01UnboundUnboundUnboundUnboundUnboundUnbound
1cjxB01UnboundUnboundUnboundUnboundUnboundUnbound
1cjxC01UnboundUnboundUnboundUnboundUnboundUnbound
1cjxD01UnboundUnboundUnboundUnboundUnboundUnbound
1t47A01UnboundUnboundUnboundUnboundUnboundUnbound
1t47B01UnboundUnboundUnboundUnboundUnboundUnbound
1sp8A01UnboundUnboundUnboundUnboundUnboundUnbound
1sp8B01UnboundUnboundUnboundUnboundUnboundUnbound
1sp8C01UnboundUnboundUnboundUnboundUnboundUnbound
1sp8D01UnboundUnboundUnboundUnboundUnboundUnbound
1sp9A01UnboundUnboundUnboundUnboundUnboundUnbound
1sp9B01UnboundUnboundUnboundUnboundUnboundUnbound
1sqdA01UnboundUnboundUnboundUnboundUnboundUnbound
1tfzA01UnboundUnboundUnboundUnboundUnboundUnbound
1cjxA02Bound:FE2UnboundUnboundUnboundUnboundIntermediate-analogue:FE2-ACT
1cjxB02Bound:FE2UnboundUnboundUnboundUnboundIntermediate-analogue:FE2-ACT
1cjxC02Bound:FE2UnboundUnboundUnboundUnboundIntermediate-analogue:FE2-ACT
1cjxD02Bound:FE2UnboundUnboundUnboundUnboundIntermediate-analogue:FE2-ACT
1t47A02Bound:FE2UnboundUnboundUnboundUnboundIntermediate-analogue:FE2-NTD
1t47B02Bound:FE2UnboundUnboundUnboundUnboundIntermediate-analogue:FE2-NTD
1sp8A02Bound:FE2UnboundUnboundUnboundUnboundUnbound
1sp8B02Bound:FE2UnboundUnboundUnboundUnboundUnbound
1sp8C02Bound:FE2UnboundUnboundUnboundUnboundUnbound
1sp8D02Bound:FE2UnboundUnboundUnboundUnboundUnbound
1sp9A02Bound:FE2UnboundUnboundUnboundUnboundUnbound
1sp9B02Bound:FE2UnboundUnboundUnboundUnboundUnbound
1sqdA02Bound:_FEUnboundUnboundUnboundUnboundUnbound
1tfzA02Bound:_FEUnboundUnboundUnboundUnboundIntermediate-analogue:_FE-869

Active-site residues
resource
PDB;1cjx
pdbCofactor-binding residues
         
1cjxA01 
1cjxB01 
1cjxC01 
1cjxD01 
1t47A01 
1t47B01 
1sp8A01 
1sp8B01 
1sp8C01 
1sp8D01 
1sp9A01 
1sp9B01 
1sqdA01 
1tfzA01 
1cjxA02HIS 161;HIS 240;GLU 322(Iron binding)
1cjxB02HIS 161;HIS 240;GLU 322(Iron binding)
1cjxC02HIS 161;HIS 240;GLU 322(Iron binding)
1cjxD02HIS 161;HIS 240;GLU 322(Iron binding)
1t47A02HIS 187;HIS 270;GLU 349(Iron binding)
1t47B02HIS 187;HIS 270;GLU 349(Iron binding)
1sp8A02HIS 219;HIS 301;GLU 387(Iron binding)
1sp8B02HIS 219;HIS 301;GLU 387(Iron binding)
1sp8C02HIS 219;HIS 301;GLU 387(Iron binding)
1sp8D02HIS 219;HIS 301;GLU 387(Iron binding)
1sp9A02HIS 226;HIS 308;GLU 394(Iron binding)
1sp9B02HIS 226;HIS 308;GLU 394(Iron binding)
1sqdA02HIS 205;HIS 287;GLU 373(Iron binding)
1tfzA02HIS 205;HIS 287;GLU 373(Iron binding)

References for Catalytic Mechanism
ReferencesSectionsNo. 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]
PubMed ID7274212
JournalEur J Biochem
Year1981
Volume117
Pages311-8
AuthorsLeinberger R, Hull WE, Simon H, Retey J
TitleSteric course of the NIH shift in the enzymic formation of homogentisic acid.
[2]
PubMed ID4027238
JournalBiochemistry
Year1985
Volume24
Pages3158-65
AuthorsPascal RA Jr, Oliver MA, Chen YC
TitleAlternate substrates and inhibitors of bacterial 4-hydroxyphenylpyruvate dioxygenase.
[3]
PubMed ID3017941
JournalJ Biol Chem
Year1986
Volume261
Pages11693-6
AuthorsBradley FC, Lindstedt S, Lipscomb JD, Que L Jr, Roe AL, Rundgren M
Title4-Hydroxyphenylpyruvate dioxygenase is an iron-tyrosinate protein.
[4]
PubMed ID1572351
JournalEur J Biochem
Year1992
Volume205
Pages459-66
AuthorsRuetschi U, Odelhog B, Lindstedt S, Barros-Soderling J, Persson B, Jornvall H
TitleCharacterization of 4-hydroxyphenylpyruvate dioxygenase. Primary structure of the Pseudomonas enzyme.
[5]
PubMed ID7597701
JournalToxicol Appl Pharmacol
Year1995
Volume133
Pages12-9
AuthorsEllis MK, Whitfield AC, Gowans LA, Auton TR, Provan WM, Lock EA, Smith LL
TitleInhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dione.
[6]
PubMed ID10465420
JournalBioorg Med Chem
Year1999
Volume7
Pages1459-65
AuthorsLing TS, Shiu S, Yang DY
TitleDesign and synthesis of 3-fluoro-2-oxo-3-phenylpropionic acid derivatives as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase from pig liver.
[7]
CommentsX-ray crystallography
PubMed ID10467142
JournalStructure Fold Des
Year1999
Volume7
Pages977-88
AuthorsSerre L, Sailland A, Sy D, Boudec P, Rolland A, Pebay-Peyroula E, Cohen-Addad C
TitleCrystal structure of Pseudomonas fluorescens 4-hydroxyphenylpyruvate dioxygenase: an enzyme involved in the tyrosine degradation pathway.
Related PDB1cjx
[8]
PubMed ID10853644
JournalBioorg Med Chem Lett
Year2000
Volume10
Pages843-5
AuthorsLin YL, Wu CS, Lin SW, Yang DY
TitleSAR studies of 2-o-substituted-benzoyl- and 2-alkanoyl-cyclohexane-1,3-diones as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
[9]
PubMed ID12067543
JournalBioorg Med Chem Lett
Year2002
Volume12
Pages1709-13
AuthorsLin YL, Huang JL, Wu CS, Liu HG, Yang DY
TitleDesign, synthesis, and evaluation of postulated transient intermediate and substrate analogues as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
[10]
PubMed ID12014960
JournalJ Med Chem
Year2002
Volume45
Pages2222-8
AuthorsWu CS, Huang JL, Sun YS, Yang DY
TitleMode of action of 4-hydroxyphenylpyruvate dioxygenase inhibition by triketone-type inhibitors.
[11]
PubMed ID12031447
JournalPhytochemistry
Year2002
Volume60
Pages281-8
AuthorsMeazza G, Scheffler BE, Tellez MR, Rimando AM, Romagni JG, Duke SO, Nanayakkara D, Khan IA, Abourashed EA, Dayan FE
TitleThe inhibitory activity of natural products on plant p-hydroxyphenylpyruvate dioxygenase.
[12]
PubMed ID12939152
JournalBiochemistry
Year2003
Volume42
Pages10238-45
AuthorsKavana M, Moran GR
TitleInteraction of (4-hydroxyphenyl)pyruvate dioxygenase with the specific inhibitor 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione.
[13]
PubMed ID15379572
JournalBiochemistry
Year2004
Volume43
Pages12331-42
AuthorsBorowski T, Bassan A, Siegbahn PE
Title4-Hydroxyphenylpyruvate dioxygenase: a hybrid density functional study of the catalytic reaction mechanism.
[14]
PubMed ID15157070
JournalBiochemistry
Year2004
Volume43
Pages6370-7
AuthorsBrownlee JM, Johnson-Winters K, Harrison DH, Moran GR
TitleStructure of the ferrous form of (4-hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis in complex with the therapeutic herbicide, NTBC.
Related PDB1t47
[15]
PubMed ID14730970
JournalBiochemistry
Year2004
Volume43
Pages663-74
AuthorsGunsior M, Ravel J, Challis GL, Townsend CA
TitleEngineering p-hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase and evidence for the proposed benzene oxide intermediate in homogentisate formation.
[16]
PubMed ID15301540
JournalBiochemistry
Year2004
Volume43
Pages10414-23
AuthorsYang C, Pflugrath JW, Camper DL, Foster ML, Pernich DJ, Walsh TA
TitleStructural basis for herbicidal inhibitor selectivity revealed by comparison of crystal structures of plant and mammalian 4-hydroxyphenylpyruvate dioxygenases.
Related PDB1sqd,1tfz
[17]
PubMed ID15070344
JournalJ Am Chem Soc
Year2004
Volume126
Pages4486-7
AuthorsNeidig ML, Kavana M, Moran GR, Solomon EI
TitleCD 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.
[18]
PubMed ID15084729
JournalPlant Physiol
Year2004
Volume134
Pages1388-400
AuthorsFritze IM, Linden L, Freigang J, Auerbach G, Huber R, Steinbacher S
TitleThe crystal structures of Zea mays and Arabidopsis 4-hydroxyphenylpyruvate dioxygenase.
Related PDB1sp8,1sp9


createdupdated
2004-10-282009-09-29
Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
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Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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