D
IPR041912

Eukaryotic phenylalanine-4-hydroxylase, catalytic domain

InterPro entry
Short nameEuk_PheOH_cat
Overlapping
homologous
superfamilies
 
domain relationships

Description

Eukaryotic phenylalanine-4-hydroxylase (eu_PheOH) is a member of the biopterin-dependent aromatic amino acid hydroxylase family of non-heme, iron(II)-dependent enzymes that also includes prokaryotic phenylalanine-4-hydroxylase (pro_PheOH), eukaryotic tyrosine hydroxylase (TyrOH) and eukaryotic tryptophan hydroxylase (TrpOH)
[2]
. The three enzymes have a three-domain structure, with an N-terminal regulatory domain (humanPheOH residues 1-142), a central catalytic domain (hPheOH residues 143-410), and a C-terminal tetramerization domain (hPheOH residues 411-452)
[4]
.

PheOH catalyzes the first and rate-limiting step in the metabolism of the amino acid L-phenylalanine (L-Phe), the hydroxylation of L-Phe to L-tyrosine (L-Tyr). It uses (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) as the physiological electron donor. The catalytic activity of the tetrameric enzyme is tightly regulated by the binding of L-Phe and BH4 as well as by phosphorylation. Mutations in the human enzyme are linked to a severe variant of phenylketonuria
[1, 3]
.

References

1.Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. Fusetti F, Erlandsen H, Flatmark T, Stevens RC. J. Biol. Chem. 273, 16962-7, (1998). View articlePMID: 9642259

2.Structure and function of the aromatic amino acid hydroxylases. Hufton SE, Jennings IG, Cotton RG. Biochem. J. 311 ( Pt 2), 353-66, (1995). View articlePMID: 7487868

3.Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations. Erlandsen H, Pey AL, Gamez A, Perez B, Desviat LR, Aguado C, Koch R, Surendran S, Tyring S, Matalon R, Scriver CR, Ugarte M, Martinez A, Stevens RC. Proc. Natl. Acad. Sci. U.S.A. 101, 16903-8, (2004). View articlePMID: 15557004

4.Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase. Erlandsen H, Bjorgo E, Flatmark T, Stevens RC. Biochemistry 39, 2208-17, (2000). View articlePMID: 10694386

Cross References

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