Linked Life Data

12590595

Source:http://linkedlifedata.com/resource/pubmed/id/12590595

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2003-2-19
pubmed:abstractText
(4-hydroxyphenyl)pyruvate dioxygenase (HPPD) catalyzes the second step in the pathway for the catabolism of tyrosine, the conversion of (4-hydroxyphenyl)pyruvate (HPP) to homogentisate (HG). This reaction involves decarboxylation, substituent migration, and aromatic oxygenation. HPPD is a member of the alpha-keto acid dependent oxygenases that require Fe(II) and an alpha-keto acid substrate to oxygenate an organic molecule. We have examined the binding of ligands to HPPD from Streptomyces avermitilis. Our data show that HPP binds to the apoenzyme and that the apo-HPPD.HPP complex does not bind Fe(II) to generate active holoenzyme. The binding of HPP, phenylpyruvate (PPA), and pyruvate to the holoenzyme produces a weak ligand charge-transfer band at approximately 500 nm that is indicative of bidentate binding of the 1-carboxylate and 2-keto pyruvate oxygen atoms to the active site metal ion. For HPPD from this organism the 4-hydroxyl group of (4-hydroxyphenyl)pyruvate is a requirement for catalysis; no turnover is observed in the presence of phenylpyruvate. The rate constant for the dissociation of Fe(II) from the holoenzyme is 0.0006 s(-)(1) and indicates that this phenomenon is not significantly relevant in steady-state turnover. The addition of HPP and molecular oxygen to the holoenzyme is formally random. The basis of the ordered bi bi steady-state kinetic mechanism previously observed by Rundgren (Rundgren, M. (1977) J. Biol. Chem. 252, 5094-9) is the 3600-fold increase in oxygen reactivity when holo-HPPD is in complex with HPP. This complex reacts with molecular oxygen with a second-order rate constant of 1.4 x 10(5) M(-)(1) s(-)(1) inducing the formation of an intermediate that decays at the catalytically relevant rate of 7.8 s(-)(1).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-Hydroxyphenylpyruvate Dioxygenase, http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxyphenylpyruvic acid, http://linkedlifedata.com/resource/pubmed/chemical/Ferene-S, http://linkedlifedata.com/resource/pubmed/chemical/Ferrous Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Ketoglutaric Acids, http://linkedlifedata.com/resource/pubmed/chemical/Oxygen, http://linkedlifedata.com/resource/pubmed/chemical/Phenylpyruvic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Pyruvic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Triazines, http://linkedlifedata.com/resource/pubmed/chemical/alpha-ketoglutaric acid, http://linkedlifedata.com/resource/pubmed/chemical/phenylpyruvic acid
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2072-80
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
(4-Hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis: the basis for ordered substrate addition.
pubmed:affiliation
Department of Chemistry, University of Wisconsin--Milwaukee, 3210 N. Cramer Street, Milwaukee, Wisconsin 53211-3029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't