Human 4‐hydroxyphenylpyruvate dioxygenase

Abstract

We report the primary structure of 4-hydroxyphenylpyruvate dioxygenase [4-hydroxyphenylpyruvate : oxygen oxidoreductase (hydroxylating, decarboxylating)]. The work is based on the isolation of cDNA clones from human liver Agtll libraries. Several overlapping clones covering the coding sequence were characterized. In parallel, peptides from four different digests of the purified protein were analysed for their amino-acid sequence. These peptide sequences covered 86% of the cDNA-derived amino-acid sequence. This gives the sequence for a polypeptide of 392 amino acids with a calculated molecular mass of 44.8 kDa.There is more than 80% identity between the human and the pig enzymes and also between these enzymes and the F antigen from rat and the two allelic forms of this antigen from mouse. The enzyme has 53% conserved amino acids and 27% identical amino acids in common with 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. P. J. 874 and 52% conserved and 28% identical residues, with a protein from Shewanella colwellinna. At the C-terminus there is 61 % identity between the seven proteins. These results indicate that these proteins are all 4-hydroxyphenylpyruvate dioxygenases. The identity of the C-terminus makes this part of the molecule a candidate for a functional role in the catalytic process. At conserved positions in all seven enzymes, there are two tyrosine residues and three histidine residues, i. e. amino acids which have been implicated as ligands for iron in 2-oxoacid-dependent dioxygenases. The gene encoding the enzyme was localized to chromosome 12q14 + qter by Southern-blot analysis of human-rodent somatic-cell hybrids.

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

“…The possible role of rat F antigen only came to light when 4HPPD from Streptomyces, human and porcine were cloned [16,18,19]. Sequence comparison showed that RFA bore a striking similarity to 4HPPD isolated from these organisms.…”

Complementation of the Arabidopsispds1Mutation with the Gene Encodingp-Hydroxyphenylpyruvate Dioxygenase

“…Genes and cDNAs encoding HPPDase have been identified from several mammalian, fungal, bacterial, and plant sources (Gershwin et al, 1987;Endo et al, 1992Endo et al, , 1995Hummel et al, 1992;Ruetschi et al, 1993;Coon et al, 1994;Denoya et al, 1994;Wilson et al, 1994;Wintermeyer et al, 1994;Kaneko et al, 1995;Wyckoff et al, 1995;Garcia et al, 1997) and show between 25% and 95% identity at the amino acid level. A computer search of the plant DNA databases, including 20,000 random Arabidopsis cDNAs (Newman et al, 1994), was conducted using human and bacterial HPPDase sequences as the query.…”

Characterization and Subcellular Compartmentation of Recombinant 4-Hydroxyphenylpyruvate Dioxygenase from Arabidopsis in Transgenic Tobacco1

“…In most organisms this enzyme activity is involved in the catabolism of the aromatic amino acid Tyr (Goodwin, 1972). All mammalian 4HPPDs purified so far behave as homodimers, with subunits of 43 to 49 kD (Wada et al, 1975;Lindblad et al, 1977;Roche et al, 1982;Endo et al, 1992;Rû etschi et al, 1993). In contrast, the Pseudomonas sp.…”

“…This reaction proceeds through an oxidative decarboxylation of the 2-oxoacid side chain of the substrate, which is accompanied by hydroxylation of the aromatic ring and a 1,2-migration of the carboxymethyl group (Jefford and Cadby, 1981). The purified enzyme was shown to contain nonheme-reduced iron, which is essential for catalytic activity (Wada et al, 1975;Lindblad et al, 1977;Roche et al, 1982;Endo et al, 1992;Rû etschi et al, 1993). This enzyme belongs to the extradiol ␣-ketoaciddependent group of dioxygenases.…”