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Information on EC 1.13.11.27 - 4-hydroxyphenylpyruvate dioxygenase and Organism(s) Homo sapiens and UniProt Accession P32754
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1.13.11.27 4-hydroxyphenylpyruvate dioxygenaseIUBMB Comments
The Pseudomonas enzyme contains one Fe3+ per mole of enzyme; the enzymes from other sources may contain essential iron or copper.
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Word Map
- 1.13.11.27
-
syncytial
- viruses
- newcastle
- hn
- paramyxovirus
- epitope
- hemagglutinin-neuraminidase
- infant
- measles
- parainfluenza
-
herbicide
-
sendai
- homogentisate
-
heptad
- hemagglutinin
- virion
-
fusogenic
- tyrosinemia
- metapneumovirus
-
prefusion
-
anti-f
-
palivizumab
-
weed
-
postfusion
- paramyxoviridae
- furin
- distemper
- ectodomains
- mumps
-
virus-cell
-
rsv-infected
-
six-helix
-
cleavability
-
formalin-inactivated
-
lasota
-
virus-neutralizing
-
virus-like
- morbillivirus
- panencephalitis
- ntbc
-
anti-rsv
-
nipah
-
velogenic
- nucleopolyhedrovirus
- drug development
- alkaptonuria
- diagnostics
-
thomsen-friedenreich
- agriculture
- environmental protection
- rinderpest
-
live-attenuated
- medicine
-
merger
- fumarylacetoacetate
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
f protein, 4-hydroxyphenylpyruvate dioxygenase, tf-ag, p-hydroxyphenylpyruvate dioxygenase, 4-hppd, 4-hydroxyphenylpyruvic acid dioxygenase, athppd, 4hppd, p-hydroxyphenylpyruvate hydroxylase, legiolysin, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
4-HPPD
-
-
-
-
4-hydroxyphenylpyruvic acid dioxygenase
-
-
-
-
4HPPD
-
-
-
-
EC 1.14.2.2
-
-
-
-
EC 1.99.1.14, formerly
-
-
-
-
F Alloantigen
-
-
-
-
F protein
-
-
-
-
F-antigen homolog
-
-
-
-
HPD
-
-
-
-
HPPD
-
-
-
-
HPPDase
-
-
-
-
Legiolysin
-
-
-
-
oxygenase, 4-hydroxyphenylpyruvate di-
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-
-
-
p-hydroxyphenylpyruvate dioxygenase
-
-
-
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p-hydroxyphenylpyruvate hydroxylase
-
-
-
-
p-hydroxyphenylpyruvate oxidase
-
-
-
-
p-hydroxyphenylpyruvic acid hydroxylase
-
-
-
-
p-hydroxyphenylpyruvic hydroxylase
-
-
-
-
p-hydroxyphenylpyruvic oxidase
-
-
-
-
T-cell reactive protein
-
-
-
-
TF-AG
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4-hydroxyphenylpyruvate + O2 = homogentisate + CO2
dioxygen reactivity and the common decarboxylation half reaction, and the hydroxylation half reaction, mechanisms, detailed overview
4-hydroxyphenylpyruvate + O2 = homogentisate + CO2
enzyme form 3: ordered bi bi mechanism where 4-hydroxyphenylpyruvate is added prior to oxygen and CO2 released before homogentisate
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decarboxylation
-
-
-
-
redox reaction
-
-
-
-
hydroxylation
-
-
-
-
side-chain migration
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
4-hydroxyphenylpyruvate:oxygen oxidoreductase (hydroxylating, decarboxylating)
The Pseudomonas enzyme contains one Fe3+ per mole of enzyme; the enzymes from other sources may contain essential iron or copper.
CAS REGISTRY NUMBER
COMMENTARY
9029-72-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-hydroxyphenylpyruvate + O2
homogentisate + CO2
the conversion of 4-hydroxyphenyl-pyruvate to homogentisate involves oxidative decarboxylation, side-chain migration and aromatic hydroxylation in a single catalytic cycle. The 4-HPPD reaction is unusual in that the 2-oxoacid and prime substrate moieties are contained within the same molecule
-
-
?
4-hydroxyphenylpyruvate + O2
homogentisate + CO2
-
-
-
-
?
4-hydroxyphenylpyruvate + O2
homogentisate + CO2
-
activity with the keto-form of 4-hydroxyphenylpyruvate is 40times higher than with the enol tautomer
-
-
?
4-hydroxyphenylpyruvate + O2
homogentisate + CO2
-
key enzyme involved in tyrosine catabolism, congenital 4-hydroxyphenylpyruvate dioxygenase deficiency is a rare, relatively benign condition known as hereditary type III tyrosinemia
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-hydroxyphenylpyruvate + O2
homogentisate + CO2
-
key enzyme involved in tyrosine catabolism, congenital 4-hydroxyphenylpyruvate dioxygenase deficiency is a rare, relatively benign condition known as hereditary type III tyrosinemia
-
-
?
4-hydroxyphenylpyruvate + O2
homogentisate + CO2
the conversion of 4-hydroxyphenyl-pyruvate to homogentisate involves oxidative decarboxylation, side-chain migration and aromatic hydroxylation in a single catalytic cycle. The 4-HPPD reaction is unusual in that the 2-oxoacid and prime substrate moieties are contained within the same molecule
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,3-diethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1H-benzo[d] imidazol-2(3H)-one
-
1,3-diethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1H-benzo[d] imidazol-2(3H)-one
-
1-benzyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
1-butyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
1-butyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
1-cyclopentyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
1-cyclopentyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
1-cyclopropyl-3-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1H-benzo[d] imidazol-2(3H)-one
-
1-ethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
1-ethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-propyl-1H-benzo[d] imidazol-2(3H)-one
-
1-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
1-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-propyl-1H-benzo[d] imidazol-2(3H)-one
-
1-tert-butyl-3-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1H-benzo[d] imidazol-2(3H)-one
-
1-tert-butyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo [d] imidazol-2(3H)-one
-
2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione
NTBC, a commercial HPPD inhibitor in clinical use
2-[3-[(2,4-dichlorophenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
-
-
2-[3-[(2,4-difluorophenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
-
-
2-[3-[(3,5-dimethylphenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
-
-
2-[3-[(4-bromo-2-fluorophenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
-
-
2-[3-[(4-bromophenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
-
-
3-(2,4-dimethylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(2,4-dimethylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(2-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
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3-(2-chloro-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
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3-(2-chloro-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
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3-(2-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
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3-(2-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(2-fluoro-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
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3-(2-fluoro-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
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3-(2-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(2-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(3,4-dichlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(3-bbromophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
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3-(3-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(3-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(3-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(3-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(3-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-bromophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-chloro-2-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-chloro-2-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-fluoro-2-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-fluoro-2-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-(4-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
-
3-ethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-isopropyl-1H-benzo[d] imidazol-2(3H)-one
-
3-ethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-propyl-1H-benzo[d] imidazol-2(3H)-one
-
3-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-isopropyl-1H-benzo[d] imidazol-2(3H)-one
-
3-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-propyl-1H-benzo[d] imidazol-2(3H)-one
-
3-hydroxy-2-[3-[(4-isopropylphenyl)methoxy]-2-nitrobenzoyl]cyclohex-2-en-1-one
-
-
3-hydroxy-2-[3-[(4-methylphenyl)methoxy]-2-nitrobenzoyl]cyclohex-2-en-1-one
-
-
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3-dipropyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-isobutyl-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-isopropyl-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-isopropyl-3-propyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1-p-tolyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1-propyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1,3-dipropyl-1H-benzo[d]imidazol-2(3H)-one
-
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-isobutyl-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-isopropyl-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-isopropyl-3-propyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1-p-tolyl-1H-benzo[d] imidazol-2(3H)-one
-
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1-propyl-1H-benzo[d] imidazol-2(3H)-one
-
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-m-tolylquinazolin-4(3H)-one
-
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-o-tolylquinazolin-4(3H)-one
-
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-p-tolylquinazolin-4(3H)-one
-
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-(2-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-(3-(trifluoromethoxy)phenyl) quinazolin-4(3H)-one
-
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-(4-(trifluoromethoxy)phenyl) quinazolin-4(3H)-one
-
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-m-tolylquinazolin-4(3H)-one
-
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-o-tolylquinazolin-4(3H)-one
-
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-p-tolylquinazolin-4(3H)-one
-
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-phenylquinazolin-4(3H)-one
-
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(2-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(3-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one
-
Cyclopropyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
enzyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
tert-butyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
-
mesotrione
molecular docking and molecular dynamics simulation estimate the interacting regions of HPPD with mesotrione using structure PDB ID 3ISQ
nitisinone
binding free energy -10.97 kcal/mol. Residues Tyr221 and Leu224 are involved in the interaction between nitisinone and HPPD
4-hydroxyphenylpyruvate
-
enzyme form 2 and 3, no substrate inhibition is observed for enzyme form 1
bathophenanthroline
-
reactivation to 30% by dialysis and to 60% by addition to Fe2+
additional information
inhibition mechanism of enzyme HPPD, detailed overview
-
additional information
structure-based design of a series of pyrazolone-quinazolone hybrids, as a class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors, synthesis, overview. Molecular modeling indicates that the interaction between the pyrazolone ring and ferrous ion, and the hydrophobic interaction of quinazolone with its surrounding residues, such as Phe347 and Phe364, contribute greatly to the high potency of these inhibitors. Compounds N-(4-methoxyphenyl)-7-nitro-2,1,3-benzoxadiazol-4-amine and 3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one can be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation
-
additional information
-
structure-based design of a series of pyrazolone-quinazolone hybrids, as a class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors, synthesis, overview. Molecular modeling indicates that the interaction between the pyrazolone ring and ferrous ion, and the hydrophobic interaction of quinazolone with its surrounding residues, such as Phe347 and Phe364, contribute greatly to the high potency of these inhibitors. Compounds N-(4-methoxyphenyl)-7-nitro-2,1,3-benzoxadiazol-4-amine and 3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one can be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation
-
additional information
synthesis of pyrazole-benzimidazolone hybrids from DNS869 and droperidol, bioevaluation of pyrazole-benzimidazolone hybrids as human 4-hydroxyphenylpyruvate dioxygenase inhibitors, overview
-
additional information
-
synthesis of pyrazole-benzimidazolone hybrids from DNS869 and droperidol, bioevaluation of pyrazole-benzimidazolone hybrids as human 4-hydroxyphenylpyruvate dioxygenase inhibitors, overview
-
additional information
formation of hHPPD-inhibitor complexes is mainly driven by van der Waals energy. Residues Ser226, Asn241, Gln265, Phe336, Phe359 and Phe364 make great contributions to binding affinities
-
additional information
-
formation of hHPPD-inhibitor complexes is mainly driven by van der Waals energy. Residues Ser226, Asn241, Gln265, Phe336, Phe359 and Phe364 make great contributions to binding affinities
-
additional information
hydrophobicity-oriented drug design strategy based on the interactions between HPPD and the commercial drug NTBC to idientify inhibitors
-
additional information
-
hydrophobicity-oriented drug design strategy based on the interactions between HPPD and the commercial drug NTBC to idientify inhibitors
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,6-dichlorophenol indophenol
-
reducing cofactor required, either ascorbate, or a combination of 2,6-dichlorophenol indophenol and glutathione
ascorbate
-
reducing cofactor required, either ascorbate, or a combination of 2,6-dichlorophenol indophenol and glutathione in presence of catalase
glutathione
-
reducing cofactor required, either ascorbate, or a combination of 2,6-dichlorophenol indophenol and glutathione in presence of catalase
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.08
4-hydroxyphenylpyruvate
pH 6.5, 37°C, wild-type enzyme and mutant DELTAG388
0.1
4-hydroxyphenylpyruvate
mutant lacking 17 N-terminal residues, pH 6.5, 37°C
0.37
4-hydroxyphenylpyruvate
mutant lacking 12 N-terminal residues, pH 6.5, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.7
4-hydroxyphenylpyruvate
mutant lacking 12 N-terminal residues, pH 6.5, 37°C
2.2
4-hydroxyphenylpyruvate
mutant lacking 17 N-terminal residues, pH 6.5, 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2
4-hydroxyphenylpyruvate
mutant lacking 12 N-terminal residues, pH 6.5, 37°C
22
4-hydroxyphenylpyruvate
mutant lacking 17 N-terminal residues, pH 6.5, 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000161
3-(2,4-dimethylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000059
3-(2,4-dimethylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000087
3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000011
3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000024
3-(2-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000109
3-(2-chloro-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00009
3-(2-chloro-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000086
3-(2-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000022
3-(2-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000081
3-(2-fluoro-4-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00017
3-(2-fluoro-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000079
3-(2-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000015
3-(2-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000025
3-(3,4-dichlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000093
3-(3-bbromophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000014
3-(3-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000173
3-(3-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00001
3-(3-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00009
3-(3-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00002
3-(3-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00013
3-(4-bromophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000018
3-(4-bromophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000177
3-(4-chloro-2-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000032
3-(4-chloro-2-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000237
3-(4-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000022
3-(4-chlorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000219
3-(4-fluoro-2-methylphenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00004
3-(4-fluoro-2-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000247
3-(4-fluorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000034
3-(4-fluorophenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000074
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-m-tolylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000248
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-o-tolylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000156
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-2-methyl-3-p-tolylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000207
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-(2-methoxyphenyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000238
6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000031
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-(3-(trifluoromethoxy)phenyl) quinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00016
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-(4-(trifluoromethoxy)phenyl) quinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000013
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-m-tolylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000058
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-o-tolylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000025
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-p-tolylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000019
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methyl-3-phenylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000038
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(2-methoxyphenyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000034
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(3-methoxyphenyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00006
6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-(4-methoxyphenyl)-2-methylquinazolin-4(3H)-one
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000068 - 0.0236
mesotrione
dependent on the system used, overview. pH and temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00094
1,3-diethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000021
1,3-diethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00013
1-benzyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00064
1-butyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00017
1-butyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00093
1-cyclopentyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00013
1-cyclopentyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00022
1-cyclopropyl-3-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00097
1-ethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00074
1-ethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-propyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000022
1-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000039
1-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-propyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00015
1-tert-butyl-3-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00099
1-tert-butyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo [d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00068
2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione
Homo sapiens
pH 7.0, 30°C, recombinant His-tagged enzyme
0.000063
2-[3-[(2,4-dichlorophenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
Homo sapiens
pH 7, 30°C
-
0.000095
2-[3-[(2,4-difluorophenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
Homo sapiens
pH 7, 30°C
-
0.000068
2-[3-[(3,5-dimethylphenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one, 2-[3-[(4-bromo-2-fluorophenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
Homo sapiens
pH 7, 30°C
-
0.000068
2-[3-[(4-bromo-2-fluorophenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
Homo sapiens
-
pH 7, 30°C
-
0.000047
2-[3-[(4-bromophenyl)methoxy]-2-nitrobenzoyl]-3-hydroxycyclohex-2-en-1-one
Homo sapiens
pH 7, 30°C
-
0.000091
2-[3-[(4-bromophenyl)methoxy]benzoyl]-3-hydroxycyclohex-2-en-1-one
Homo sapiens
pH 7, 30°C
-
0.00097
3-ethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-isopropyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00088
3-ethyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-propyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000064
3-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-isopropyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000022
3-ethyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-propyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00007
3-hydroxy-2-[3-[(4-isopropylphenyl)methoxy]-2-nitrobenzoyl]cyclohex-2-en-1-one, 3-hydroxy-2-[3-[(4-methylphenyl)methoxy]-2-nitrobenzoyl]cyclohex-2-en-1-one
Homo sapiens
pH 7, 30°C
-
0.00007
3-hydroxy-2-[3-[(4-methylphenyl)methoxy]-2-nitrobenzoyl]cyclohex-2-en-1-one
Homo sapiens
-
pH 7, 30°C
-
0.00072
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,3-dipropyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00271
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-isobutyl-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00094
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-isopropyl-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00119
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1-isopropyl-3-propyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00099
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1-p-tolyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00103
5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1-propyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00004
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1,3-dipropyl-1H-benzo[d]imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00014
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-isobutyl-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000061
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-isopropyl-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000077
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-1-isopropyl-3-propyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00025
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1-p-tolyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.000059
5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1-propyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.0001
Cyclopropyl-5-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
0.00067
enzyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-methyl-1H-benzo[d] imidazol-2(3H)-one
Homo sapiens
recombinant His-tagged enzyme, pH 7.0, 30°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.04
purified recombinant mutant R378K, pH 6.5, 37°C, homogentisate production
0.2
purified recombinant mutant E254D, pH 6.5, 37°C, homogentisate production
2.8
purified recombinant wild-type enzyme, pH 6.5, 37°C, homogentisate production
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
-
and a second optimum at pH 5.1 for enzyme form 1 and 2, and at pH 4.6 for enzyme form 3
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
no enzymatic activity in any tissue other than liver and kidney
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
HPD promotes tyrosine catabolism leading to increased acetyl-CoA levels, the source of histone acetylation, and also stimulates histone deacetylase 10 translocation from the nucleus into the cytoplasm mediated by tumor suppressor liver kinase B1-AMP-activated protein kinase signaling
additional information
evolution
the enzyme belongs to the non-haem Fe(II)/2-oxoacid-dependent oxygenase superfamily, which couples the oxidative decarboxylation of a 2-oxoacid (most commonly a-ketoglutarate) to the oxidation of the prime substrate
evolution
4-hydroxyphenylpyruvate dioxygenase (HPPD) and hydroxymandelate synthase (HMS, EC 1.13.11.46) are outliers within the 2-oxo acid dependent oxygenase (aKAO) family. HPPD and HMS catalyze the chemistry of the majority of enzymes within the aKAO family but are clearly mechanistically convergent, having a grossly different structural topology. Some of the unique characteristics of HPPD and HMS have elucidated select parts of the catalytic cycle that are obscured in other family members. Moreover, the inhibitory chemistry of HPPD is a phenomenon with ever-expanding relevance across all kingdoms of life
malfunction
deficiency in active 4-HPPD in humans results in type III tyrosinemia, a rare autosomal recessive disorder
malfunction
inhibition of HPPD can effectively alleviate the symptoms of type I tyrosinemia
malfunction
neutrophil preparations from a patient with tyrosinemia type III, with inherited deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPPD), exhibit a far higher NO release than controls, when NO is estimated in terms of nitrite content in the suspending media. L-tyrosine increases nitrite release and accumulation in suspending media of U-937 cells, a human monoblast-like lymphoma cell line which displays many characteristics of macrophages, including the expression of inducible and endothelial nitric oxide synthases. The increase of nitrite release by patient's neutrophils might be related to the presence of high L-tyrosine concentrations in the blood samples rather than to HPPD deficiency of in these cells
metabolism
enzyme 4-HPPD catalyzes the second step in the pathway of tyrosine catabolism, the conversion of 4-hydroxyphenyl-pyruvate to homogentisate
metabolism
4-ydroxyphenylpyruvate dioxygenase (HPPD) is an essential enzyme in tyrosine catabolism
metabolism
hydroxyphenylpyruvate dioxygenase catalyzes the second step in the pathway of L-tyrosine catabolism, the conversion of 4-hydroxyphenylpyruvate to homogentisate
additional information
the disordered C-terminal tail of the enzyme, which is extended C-terminus compared to other 4-HPPD enzymes, plays an important role in catalysis with a critical role of residue Q375 in orientating the tail and ensuring the conformation of the terminal alpha-helix to maintain the integrity of the active site for catalysis. The active site of 4-HPPD is enclosed by a C-terminal alpha-helix which is assumed to function as a gate which controls access of substrate. Interactions provided by Q375 to hold the terminal helix and the tail in proper position are critical for isolating the active site from solvent during catalysis, enzyme structure modeling, overview
additional information
-
the disordered C-terminal tail of the enzyme, which is extended C-terminus compared to other 4-HPPD enzymes, plays an important role in catalysis with a critical role of residue Q375 in orientating the tail and ensuring the conformation of the terminal alpha-helix to maintain the integrity of the active site for catalysis. The active site of 4-HPPD is enclosed by a C-terminal alpha-helix which is assumed to function as a gate which controls access of substrate. Interactions provided by Q375 to hold the terminal helix and the tail in proper position are critical for isolating the active site from solvent during catalysis, enzyme structure modeling, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). HPPD_HUMAN
393
0
44934
Swiss-Prot
other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
five residues of the N-terminus in recombinant 4-HPPD are TTYSD
additional information
-
five residues of the N-terminus in recombinant 4-HPPD are TTYSD
additional information
-
the multiple enzyme forms are not interconvertible by oxidation, reduction, pyridine inactivation, metal chelator treatment, or treatment with neuraminidase
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
recombinant enzyme can be phosphorylated in human AMA cells, phosphorylation is not indispensable for activity
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
comparison of Arabidopsis thaiana and human enzyme. In human, the carboxyl group of substrate 4-hydroxyphenylpyruvate interacts by a H-bond network formed by Gln334, metal-binding ligand Glu349, and Asn363 in the C-terminal helix. The 4-hydroxyl group of the substrate interacts with Gln251 and Gln265
homology modeling of structure and docking of inhibitors. Each molecule consists of 9 alpha-helices and 2 twisted barrel-like beta-sheets, and the active site is located at the C-terminus
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E254D
site-directed mutagenesis, the mutant shows 5% remaining activity compared to the wild-type enzyme
L224A
binding ability of the mutant to nitisinone is significantly weaker than that of wild-type
Q375N
site-directed mutagenesis, the mutant shows that a solvent accessible channel opens to the putative substrate binding site, suggesting this is responsible for the complete loss of activity, modeling, overview. Inactive mutant
R378K
site-directed mutagenesis, the mutant shows 5% remaining activity compared to the wild-type enzyme
Y221A
binding ability of the mutant to nitisinone is significantly weaker than that of wild-type
additional information
additional information
human 4-HPPD possesses an extended C-terminus compared to other 4-HPPD enzymes. Successive truncation of the disordered tail which follows the final alpha-helix results in no changes in the Km value for 4-HPP substrate but the kcat values are significantly reduced by ca. 25 to 50%. The different conformation of E254, R378 and Q375 in the final helix might be the cause of the activity loss
additional information
-
human 4-HPPD possesses an extended C-terminus compared to other 4-HPPD enzymes. Successive truncation of the disordered tail which follows the final alpha-helix results in no changes in the Km value for 4-HPP substrate but the kcat values are significantly reduced by ca. 25 to 50%. The different conformation of E254, R378 and Q375 in the final helix might be the cause of the activity loss
additional information
construction of a nanobiosensor based on HPPD for mesotrione detection. The atomic force microscope tip functionalization with HPPD immobilized in self-assembled monolayers is confirmed by fluorescence microscopy and atomic force spectroscopy. The cross-linker N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride is responsible for properly preserving the enzyme on the tip
additional information
upon removal of the 12 N-terminal residues, the kcat/Km decreases 8fold compared to wild-type. The wild-type level of activity is retained in a mutant missing the 17 N-terminal residues, with a kcat/Km 11fold higher than that of the mutant lacking 12 N-terminal residues, however, the structural stability of this mutant is lower than that of wild type
additional information
-
upon removal of the 12 N-terminal residues, the kcat/Km decreases 8fold compared to wild-type. The wild-type level of activity is retained in a mutant missing the 17 N-terminal residues, with a kcat/Km 11fold higher than that of the mutant lacking 12 N-terminal residues, however, the structural stability of this mutant is lower than that of wild type
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-60°C, pH 7.5, 3 months, 20% loss of activity when enzyme concentration is 0.5 g/L in Tris/HCl buffer, no loss of activity after 4 years when enzyme concentration is 5 g/l
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme 15fold from Escherichia coli by anion-exchange and hydrophobic interaction chromatography, and gel filtration
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and ultrafiltration
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and ultrafiltration
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and ultrafiltration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, human enzyme expression in Escherichia coli
gene HPD, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3)
vaccinia virus-based expression in human AMA cells and expression in Escherichia coli
-
gene HPD, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3)
gene HPD, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3)
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
colorimetric bacterial whole-cell screening system based on the degradation of tyrosine through 4-hydroxyphenylpyruvate into homogentisate by human HPD expressed in Escherichia coli and subsequent production of a soluble melanin-like pigment. The addition of prototypical beta-triketone HPD inhibitors decreases pigment production in a dose-dependent manner with increasing inhibitor concentrations. The high-throughput screening assay shows plate uniformity, signal variability and spatial uniformity assessment
diagnostics
the enzyme can be used for enzyme-based sensors for monitoring herbicides used in agriculture, i.e. mesotrione. Compared to the standard sensors, biosensors have assorted advantages, such as practicality, quick response, low cost, and high sensitivity. A nanobiosensor is developed based on HPPD for mesotrione detection
drug development
environmental protection
the enzyme can be used for enzyme-based sensors for monitoring herbicides used in agriculture, i.e. mesotrione. Compared to the standard sensors, biosensors have assorted advantages, such as practicality, quick response, low cost, and high sensitivity. A nanobiosensor is developed based on HPPD for mesotrione detection
medicine
drug development
4-hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine catabolism, is an important target for treating type I tyrosinemia
drug development
the enzyme is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism
drug development
the human enzyme is a target for drug development in treatment of type 1 tyrosinemia, alkaptonuria, and hawkinsinuria, overvuew
medicine
4-hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine catabolism, is an important target for treating type I tyrosinemia
medicine
compounds N-(4-methoxyphenyl)-7-nitro-2,1,3-benzoxadiazol-4-amine and 3-(2-bromo-4-methylphenyl)-6-(5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-2-methylquinazolin-4(3H)-one can be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation
medicine
HPD is highly expressed in lung cancer and expression correlates with poor prognosis in lung cancer patients. Suppressed HPD expression is sufficient to decrease oxidative pentose phosphate pathway flux, leading to reduced RNA biosynthesis and enhanced reactive oxygen species level, attenuated cancer cell proliferation, and tumor growth
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lindstedt, S.; Odelhoeg, B.
4-Hydroxyphenylpyruvate dioxygenase from human liver
Methods Enzymol.
142
139-142
1987
Homo sapiens
Lindblad, B.; Lindstedt, G.; Lindstedt, S.; Rundgren, M.
Purification and some properties of human 4-hydroxyphenylpyruvate dioxygenase (I)
J. Biol. Chem.
252
5073-5084
1977
Homo sapiens
Rundgren, M.
Multiple forms of human 4-hydroxyphenylpyruvate dioxygenase (II)
J. Biol. Chem.
252
5085-5093
1977
Homo sapiens
Rundgren, M.
Steady state kinetics of 4-hydroxyphenylpyruvate dioxygenase from human liver (III)
J. Biol. Chem.
252
5094-5099
1977
Homo sapiens
Abbott, M.T.; Udenfriend, S.
alpha-Ketoglutarate-coupled dioxygenases
Mol. Mech. Oxygen Activ. (Hayaishi, O., ed.) Academic Press, New York
167-214
1974
Bos taurus, Canis lupus familiaris, Cavia porcellus, Gallus gallus, Oryctolagus cuniculus, Frog, Homo sapiens, Platyrrhini, Oncorhynchus mykiss, Didelphidae, Rattus norvegicus, Sus scrofa
-
Aarenstrup, L.; Falch, A.M.; Jakobsen, K.K.; Neve, S.; Henriksen, L.L.; Tommerup, N.; Leffers, H.; Kristiansen, K.
Expression and post-translational modification of human 4-hydroxy-phenylpyruvate dioxygenase
Cell Biol. Int.
26
615-625
2002
Homo sapiens
Lin, J.F.; Sheih, Y.L.; Chang, T.C.; Chang, N.Y.; Chang, C.W.; Shen, C.P.; Lee, H.J.
The interactions in the carboxyl terminus of human 4-hydroxyphenylpyruvate dioxygenase are critical to mediate the conformation of the final helix and the tail to shield the active site for catalysis
PLoS ONE
8
e69733
2013
Homo sapiens (P32754), Homo sapiens
Moran, G.
4-Hydroxyphenylpyruvate dioxygenase and hydroxymandelate synthase exemplars of the alpha-keto acid dependent oxygenases
Arch. Biochem. Biophys.
544
58-68
2014
Pseudomonas fluorescens, Paracoccidioides brasiliensis, Homo sapiens (P32754), Arabidopsis thaliana (P93836), Streptomyces avermitilis (Q53586), Streptomyces avermitilis ATCC 31267 (Q53586)
Salerno, C.; Zicari, A.; Mari, E.; D'Eufemia, P.
Scavenging properties of neutrophil 4-hydroxyphenylpyruvate dioxygenase are based on a hypothesis that does not stand up to scrutiny
Biomed. Pharmacother.
68
1045-1048
2014
Homo sapiens (P32754), Homo sapiens
Xu, Y.L.; Lin, H.Y.; Cao, R.J.; Ming, Z.Z.; Yang, W.C.; Yang, G.F.
Pyrazolone-quinazolone hybrids a novel class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors
Bioorg. Med. Chem.
22
5194-5211
2014
Homo sapiens (P32754), Homo sapiens
Xu, Y.L.; Lin, H.Y.; Ruan, X.; Yang, S.G.; Hao, G.F.; Yang, W.C.; Yang, G.F.
Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4-hydroxyphenylpyruvate dioxygenase inhibitors
Eur. J. Med. Chem.
92
427-438
2015
Homo sapiens (P32754), Homo sapiens
Garcia, P.; Moreau, A.; Ierich, J.; Vig, A.; Higa, A.; Oliveira, G.; Abdalla, F.; Hausen, M.; Leite, F.
A nanobiosensor based on 4-hydroxyphenylpyruvate dioxygenase enzyme for mesotrione detection
IEEE Sens. J.
15
2106-2113
2015
Homo sapiens (P32754)
-
Huang, C.W.; Hwang, C.C.; Chang, Y.L.; Liu, J.T.; Wu, S.P.; Huang, K.L.; Huang, W.M.; Lee, H.J.
Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase
Biochem. J.
478
2201-2215
2021
Homo sapiens (P32754), Homo sapiens
Shan, C.; Lu, Z.; Li, Z.; Sheng, H.; Fan, J.; Qi, Q.; Liu, S.; Zhang, S.
4-Hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis
Cell Death Dis.
10
525
2019
Homo sapiens (P32754), Homo sapiens
Ndikuryayo, F.; Kang, W.M.; Wu, F.X.; Yang, W.C.; Yang, G.F.
Hydrophobicity-oriented drug design (HODD) of new human 4-hydroxyphenylpyruvate dioxygenase inhibitors
Eur. J. Med. Chem.
166
22-31
2019
Homo sapiens (P32754), Homo sapiens
Liu, Y.; Zhao, L.; Ye, T.; Gao, S.; Li, J.; Ye, F.; Fu, Y.
Identification of key residues determining the binding specificity of human 4-hydroxyphenylpyruvate dioxygenase
Eur. J. Pharm. Sci.
154
105504
2020
Homo sapiens (P32754), Homo sapiens
Feng, A.N.; Huang, C.W.; Lin, C.H.; Chang, Y.L.; Ni, M.Y.; Lee, H.J.
Role of the N-terminus in human 4-hydroxyphenylpyruvate dioxygenase activity
J. Biochem.
167
315-322
2020
Homo sapiens (P32754), Homo sapiens
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