InterPro domain: IPR041736

HppD and HmaS are non-heme iron-dependent dioxygenases, which modify a common substrate, 4-hydroxyphenylpyruvate (HPP), but yield different products. HPPD catalyzes the second reaction in tyrosine catabolism, the conversion of HPP to homogentisate (2,5-dihydroxyphenylacetic acid, HG). HmaS converts HPP to 4-hydroxymandelate, a committed step in the formation of hydroxyphenylglycerine, a structural component of nonproteinogenic macrocyclic peptide antibiotics, such as vancomycin [ 1 , 2 ]. If the emphasis is on catalytic chemistry, HPPD and HmaS are classified as members of a large family of alpha-keto acid dependent mononuclear non-heme iron oxygenases most of which require Fe(II), molecular oxygen, and an alpha-keto acid (typically alpha-ketoglutarate) to either oxygenate or oxidize a third substrate. Both enzymes are exceptions in that they require two, instead of three, substrates, do not use alpha-ketoglutarate, and incorporate both atoms of dioxygen into the aromatic product [ 3 ]. Both HPPD and HmaS exhibit duplicate beta barrel topology in their N- and C-terminal domains which share sequence similarity, suggestive of a gene duplication. Each protein has only one catalytic site located in at the C-terminal domain [ 4 ]. This entry represents the N-terminal domain.

1. 4-Hydroxyphenylpyruvate dioxygenase. Arch. Biochem. Biophys. 433, 117-28
2. Structural basis for herbicidal inhibitor selectivity revealed by comparison of crystal structures of plant and mammalian 4-hydroxyphenylpyruvate dioxygenases. Biochemistry 43, 10414-23
3. We two alone will sing: the two-substrate alpha-keto acid-dependent oxygenases. Curr Opin Chem Biol 13, 443-50
4. Human 4-hydroxyphenylpyruvate dioxygenase. Primary structure and chromosomal localization of the gene. Eur. J. Biochem. 213, 1081-9