Biopterin-dependent aromatic amino acid hydroxylase

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Biopterin_H
PDB 1mmt EBI.jpg
crystal structure of ternary complex of the catalytic domain of human phenylalanine hydroxylase (fe(ii)) complexed with tetrahydrobiopterin and norleucine
Identifiers
Symbol Biopterin_H
Pfam PF00351
InterPro IPR019774
PROSITE PDOC00316
SCOP 1toh
SUPERFAMILY 1toh

In molecular biology, the biopterin-dependent aromatic amino acid hydroxylases (abbreviated AAAH) constitute a family of aromatic amino acid hydroxylases, including phenylalanine, tyrosine and tryptophan hydroxylases. These enzymes are all rate-limiting catalysts for important metabolic pathways.[1] The proteins are structurally and functionally related, each containing iron, and catalysing ring hydroxylation of aromatic amino acids, using tetrahydrobiopterin (BH4) as a substrate. All are regulated by phosphorylation at serines in their N-termini. It has been suggested that the proteins each contain a conserved C-terminal catalytic (C) domain and an unrelated N-terminal regulatory (R) domain. It is possible that the R domains arose from genes that were recruited from different sources to combine with the common gene for the catalytic core. Thus, by combining with the same C domain, the proteins acquired the unique regulatory properties of the separate R domains.

Enzymes belonging to this family include: phenylalanine-4-hydroxylase from Chromobacterium violaceum where it is copper-dependent; it is iron-dependent in Pseudomonas aeruginosa, phenylalanine-4-hydroxylase catalyzes the conversion of phenylalanine to tyrosine. In humans, deficiencies are the cause of phenylketonuria, the most common inborn error of amino acid metabolism,[2] tryptophan 5-hydroxylase catalyzes the rate-limiting step in serotonin biosynthesis: the conversion of tryptophan to 5-hydroxy-L-tryptophan and tyrosine 3-hydroxylase catalyzes the rate limiting step in catecholamine biosynthesis: the conversion of tyrosine to 3,4-dihydroxy-L-phenylalanine.

Human biosynthesis pathway for trace amines and catecholamines[5]

In humans, catecholamines and phenethylaminergic trace amines are derived from the amino acid phenylalanine.

References[edit]

  1. ^ Grenett HE, Ledley FD, Reed LL, Woo SL (August 1987). "Full-length cDNA for rabbit tryptophan hydroxylase: functional domains and evolution of aromatic amino acid hydroxylases". Proc. Natl. Acad. Sci. U.S.A. 84 (16): 5530–4. doi:10.1073/pnas.84.16.5530. PMC 298896. PMID 3475690. 
  2. ^ Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC (December 1997). "Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria". Nat. Struct. Biol. 4 (12): 995–1000. doi:10.1038/nsb1297-995. PMID 9406548. 
  3. ^ Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186. 
  4. ^ Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375. 
  5. ^ [3][4]

This article incorporates text from the public domain Pfam and InterPro IPR019774