[18] 4-Hydroxyphenylpyruvate dioxygenase from pig liver

Buckthal, David J.; Roche, P.; Moorehead, Thomas J.; Forbes, Brian J.; Hamilton, Gordon A.

doi:10.1016/s0076-6879(87)42020-x

Cited by 23 publications

(7 citation statements)

References 5 publications

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“…The apparent Michaelis constant, K m , for p -HPP and the apparent specific activity, V m , were on the order of 7.5 ± 2.5 μM and 2.0 ± 0.3 μmol of O 2 min -1 (mg of purified HPPD) -1 , respectively. The high specific activity determined was in the range of specific activities observed for purified HPPD from other organisms ( − ). Moreover, the K m value for p -HPP corresponds well with that determined for plant HPPDs ( 19 , 20 , 29 ).…”

Section: Resultsmentioning

confidence: 71%

“…A deficiency in HPPD activity is responsible for a hereditary disease in humans, called hypertyrosinaemia (). Therefore, a thorough study of mammalian and bacterial HPPDs was engaged, and this enzyme activity was purified from many different species, including rat (), avian (), pig ( , ), human (), and Pseudomonas (). All mammalian HPPDs behave as homodimers of 43−49 kDa subunits, whereas the Pseudomonas enzyme is a homotetramer with 41 kDa subunits.…”

mentioning

confidence: 99%

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Inhibition of p-Hydroxyphenylpyruvate Dioxygenase by the Diketonitrile of Isoxaflutole: A Case of Half-Site Reactivity

2000

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p-Hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes the formation of homogentisate from p-hydroxyphenylpyruvate and molecular oxygen. In plants, this enzyme is the molecular target of new families of very active bleaching herbicides. In the study presented here, we report for the first time on the purification to homogeneity of a plant enzyme, as obtained from recombinant Escherichia coli cells expressing a cDNA encoding carrot HPPD. The purified enzyme allowed us to carry out a detailed characterization of the inhibitory properties of a diketonitile (DKN), the active inhibitor formed from the benzoylisoxazole herbicide isoxaflutole. Inhibition kinetic analyses confirmed that DKN exerts a slow and tight-binding inhibition of HPPD, competitive with respect to the p-hydroxyphenylpyruvate substrate. The stoichiometry of DKN binding to HPPD determined by kinetic analyses or by direct binding of [(14)C]DKN revealed a half-site reactivity of DKN.

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Section: Resultsmentioning

confidence: 71%

mentioning

confidence: 99%

Inhibition of p-Hydroxyphenylpyruvate Dioxygenase by the Diketonitrile of Isoxaflutole: A Case of Half-Site Reactivity

2000

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“…Enzyme Purification and Assay. 4-HPPD was purified from pig liver by the method of Hamilton with a specific activity of 0.1 μmol min -1 mg -1 . The protein concentration was determined by the BCA method.…”

Section: Methodsmentioning

confidence: 99%

Mode of Action of 4-Hydroxyphenylpyruvate Dioxygenase Inhibition by Triketone-type Inhibitors

Huang

Sun

et al. 2002

J. Med. Chem.

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A series of 2-(2-nitrobenzoyl)cyclohexane-1,3-dione analogues (1-9) were designed, synthesized, and evaluated for inhibition of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), a key enzyme involved in the catabolism of tyrosine which catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. The correlations between the results of enzyme inhibition, ferric chloride tests, and the conformational analysis suggested that the tight binding between triketone-type inhibitors and 4-HPPD is likely due to chelation of the enzyme-bound ferric iron with the enol tautomer of 1,3-diketone moiety of the triketones. The presence of a 2-carbonyl group in the triketone is an essential structural feature for potent 4-HPPD inhibition. Modification of the 3-carbonyl group of triketone moiety to other functionality will reduce the overall planarity and thus prevent keto-enol tautomerization, resulting in a decrease or lack of inhibition activity.

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“…The enzyme has been purified from porcine [1], human [2] and avian livers [3] as well as Pseudomonas sp. [4].…”

Section: -Hydroxyphenylpyruvate Dioxygenase (4hppd)mentioning

confidence: 99%

“…4-Hydroxyphenylpyruvate dioxygenase (4HPPD) is an enzyme involved in the metabolism of tyrosine, converting 4hydroxyphenylpyruvate (4HPP) to homogentisate through decarboxylation and hydroxylation. The enzyme has been purified from porcine [1], human [2] and avian livers [3] as well as Pseudomonas sp. [4].…”

Section: Introductionmentioning

confidence: 99%

The C‐terminal of rat 4‐hydroxyphenylpyruvate dioxygenase is indispensable for enzyme activity

Lee¹,

Zhang²,

MacKinnon³

et al. 1996

FEBS Letters

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We have cloned and overexpressed rat 4-hydroxyphenylpyruvate dioxygenase (4HPPD) in Escherichia coilThe soluble, active recombinant enzyme was shown to contain both 4HPPD and ¢x-ketoisocaproate dioxygenase (¢zKICD) activity. However, upon truncation of the 14 amino acids at the Cterminus by site-directed mutagenesis, the resulting mutant enzyme (rat F antigen) exhibited complete loss of 4HPPD and ff~KICD activities. This finding suggests that the C-terminal extension domain plays an essential role in the catalytic activity of the enzyme.Key words: 4-Hydroxyphenylpyruvate dioxygenase; c¢-Ketoisocaproate dioxygenase; Rat F antigen; C-terminal domain Database analysis and multiple alignment of amino acid sequences revealed that rat F antigen (RFA) exhibits a high degree of homology (> 90%) with 4HPPD from a variety of species. RFA is a protein of about 43 kDa found predominantly in the hepatic cytoplasm of mammals. First identified in 1968, it has been extensively studied as a model of tolerance but to date, its function is still unknown [10 12].

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[18] 4-Hydroxyphenylpyruvate dioxygenase from pig liver

Cited by 23 publications

References 5 publications

Inhibition of p-Hydroxyphenylpyruvate Dioxygenase by the Diketonitrile of Isoxaflutole: A Case of Half-Site Reactivity

Inhibition of p-Hydroxyphenylpyruvate Dioxygenase by the Diketonitrile of Isoxaflutole: A Case of Half-Site Reactivity

Mode of Action of 4-Hydroxyphenylpyruvate Dioxygenase Inhibition by Triketone-type Inhibitors

The C‐terminal of rat 4‐hydroxyphenylpyruvate dioxygenase is indispensable for enzyme activity

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