 |
InterPro: IPR018301 Aromatic amino acid hydroxylase, iron/copper binding site
Protein matches
|
UniProtKB Matches: 413 proteins |
|
|
Accession
|
IPR018301 ArAA_hydroxylase_Fe/CU_BS |
|
Type
|
Binding_site |
|
Signatures
|
|
|
InterPro Relationships
|
|
Found in
|
IPR001273 Aromatic amino acid hydroxylase
IPR005960 Phenylalanine-4-hydroxylase, monomeric form
IPR005961 Phenylalanine-4-hydroxylase, tetrameric form
IPR005962 Tyrosine 3-monooxygenase
IPR005963 Tryptophan 5-monooxygenase
IPR019773 Tyrosine 3-monooxygenase-like
IPR019774 Aromatic amino acid hydroxylase, C-terminal
|
|
GO Term annotation
|
|
Process
|
GO:0009072 aromatic amino acid family metabolic process
GO:0055114 oxidation reduction
|
|
Function
|
GO:0004497 monooxygenase activity
GO:0005506 iron ion binding
|
|
InterPro annotation
|
|
 Entry Details in BioMart
|
|
Abstract
|
Phenylalanine, tyrosine and tryptophan hydroxylases constitute a family of
tetrahydrobiopterin-dependent aromatic amino acid hydroxylases, all of which are
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 tetra-hydrobiopterin (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.
A variety of enzymes belong to this family that includes, 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 3-hydroxy-anthranilate and tyrosine 3-hydroxylase catalyzes the rate limiting step in catecholamine biosynthesis:
the conversion of tyrosine to 3,4-dihydroxy-L-phenylalanine.
Enzymes that belong to this family are functionally as well as structurally related [3]. Their size ranges from 260 residues for bacterial PAH, to about 500 residues for eukaryotic PAH, TYH and TRH. The signature pattern used in this entry is to a conserved region in the central part of these enzymes, which contains two conserved histidines that are involved in the binding to iron or copper [4].
|
|
Structural links
|
|
|
Database links
|
|
|
Publications
|
|
1.
|
Grenett HE, Ledley FD, Reed LL, Woo SL.
Full-length cDNA for rabbit tryptophan hydroxylase: functional domains and evolution of aromatic amino acid hydroxylases.
Proc. Natl. Acad. Sci. U.S.A. 84 5530-4 1987
[PubMed: 3475690]
http://ukpmc.ac.uk/picrender.cgi?tool=EBI&pubmedid=3475690&action=stream&blobtype=pdf
|
|
2.
|
Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC.
Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria.
Nat. Struct. Biol. 4 995-1000 1997
[PubMed: 9406548]
http://dx.doi.org/10.1038/nsb1297-995
|
|
3.
|
Hoang L, Byck S, Prevost L, Scriver CR.
PAH Mutation Analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locus.
Nucleic Acids Res. 24 127-31 1996
[PubMed: 8594560]
http://dx.doi.org/10.1093/nar/24.1.127
|
|
4.
|
Goodwill KE, Sabatier C, Marks C, Raag R, Fitzpatrick PF, Stevens RC.
Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases.
Nat. Struct. Biol. 4 578-85 1997
[PubMed: 9228951]
http://dx.doi.org/10.1038/nsb0797-578
|
|
Additional Reading
|
|
Onishi A, Liotta LJ, Benkovic SJ.
Cloning and expression of Chromobacterium violaceum phenylalanine hydroxylase in Escherichia coli and comparison of amino acid sequence with mammalian aromatic amino acid hydroxylases.
J. Biol. Chem. 266 1991 18454-9
[PubMed: 1655752]
http://intl.jbc.org/cgi/content/abstract/266/28/18454
|
|
|
Andersen OA, Stokka AJ, Flatmark T, Hough E.
2.0A resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine or L-norleucine: substrate specificity and molecular motions related to substrate binding.
J. Mol. Biol. 333 2003 747-57
[PubMed: 14568534]
http://dx.doi.org/10.1016/j.jmb.2003.09.004
|
|
|
Leiros HK, Pey AL, Innselset M, Moe E, Leiros I, Steen IH, Martinez A.
Structure of phenylalanine hydroxylase from Colwellia psychrerythraea 34H, a monomeric cold active enzyme with local flexibility around the active site and high overall stability.
J. Biol. Chem. 282 2007 21973-86
[PubMed: 17537732]
http://dx.doi.org/10.1074/jbc.M610174200
|
|
|
Erlandsen H, Kim JY, Patch MG, Han A, Volner A, Abu-Omar MM, Stevens RC.
Structural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates.
J. Mol. Biol. 320 2002 645-61
[PubMed: 12096915]
http://dx.doi.org/10.1016/S0022-2836(02)00496-5
|
|
|
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.
Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations.
Proc. Natl. Acad. Sci. U.S.A. 101 2004 16903-8
[PubMed: 15557004]
http://dx.doi.org/10.1073/pnas.0407256101
|
|
|
Zhao G, Xia T, Song J, Jensen RA.
Pseudomonas aeruginosa possesses homologues of mammalian phenylalanine hydroxylase and 4 alpha-carbinolamine dehydratase/DCoH as part of a three-component gene cluster.
Proc. Natl. Acad. Sci. U.S.A. 91 1994 1366-70
[PubMed: 8108417]
http://ukpmc.ac.uk/articlerender.cgi?tool=EBI&pubmedid=8108417
|
|
|
Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC.
Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin.
Biochemistry 41 2002 12569-74
[PubMed: 12379098]
http://dx.doi.org/10.1021/bi026561f
|
|
|
InterPro 23.1
|
