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37  structures 829  species 1  interaction 1616  sequences 13  architectures

Family: Biopterin_H (PF00351)

Summary: Biopterin-dependent aromatic amino acid hydroxylase

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This is the Wikipedia entry entitled "Biopterin-dependent aromatic amino acid hydroxylase". More...

Biopterin-dependent aromatic amino acid hydroxylase Edit Wikipedia article

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.

Trace amine and catecholamine biosynthesis in humans

AAAH is an important family of enzymes in the trace amine and catecholamine pathways of phenylalanine.

References

  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. 

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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Biopterin-dependent aromatic amino acid hydroxylase Provide feedback

This family includes phenylalanine-4-hydroxylase, the phenylketonuria disease protein.

Literature references

  1. Grenett HE, Ledley FD, Reed LL, Woo SL; , Proc Natl Acad Sci U S A 1987;84:5530-5534.: Full-length cDNA for rabbit tryptophan hydroxylase: functional domains and evolution of aromatic amino acid hydroxylases. PUBMED:3475690 EPMC:3475690

  2. Onishi A, Liotta LJ, Benkovic SJ; , J Biol Chem 1991;266:18454-18459.: Cloning and expression of Chromobacterium violaceum phenylalanine hydroxylase in Escherichia coli and comparison of amino acid sequence with mammalian aromatic amino acid hydroxylases. PUBMED:1655752 EPMC:1655752

  3. Zhao G, Xia T, Song J, Jensen RA; , Proc Natl Acad Sci U S A 1994;91:1366-1370.: Pseudomonas aeruginosa possesses homologues of mammalian phenylalanine hydroxylase and 4 alpha-carbinolamine dehydratase/DCoH as part of a three-component gene cluster. PUBMED:8108417 EPMC:8108417

  4. Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC; , Nat Struct Biol 1997;4:995-1000.: Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria. PUBMED:9406548 EPMC:9406548


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR019774

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 [PUBMED:3475690]. 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 [PUBMED:9406548], 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.

Gene Ontology

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Domain organisation

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Alignments

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(6)
Full
(1616)
Representative proteomes NCBI
(1403)
Meta
(197)
RP15
(167)
RP35
(254)
RP55
(398)
RP75
(525)
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  Seed
(6)
Full
(1616)
Representative proteomes NCBI
(1403)
Meta
(197)
RP15
(167)
RP35
(254)
RP55
(398)
RP75
(525)
Alignment:
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  Seed
(6)
Full
(1616)
Representative proteomes NCBI
(1403)
Meta
(197)
RP15
(167)
RP35
(254)
RP55
(398)
RP75
(525)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Curation and family details

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Curation View help on the curation process

Seed source: Prosite
Previous IDs: biopterin_H;
Type: Domain
Author: Finn RD
Number in seed: 6
Number in full: 1616
Average length of the domain: 213.20 aa
Average identity of full alignment: 33 %
Average coverage of the sequence by the domain: 70.19 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.0 22.0
Trusted cut-off 24.6 24.6
Noise cut-off 19.3 19.3
Model length: 332
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

Biopterin_H

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Biopterin_H domain has been found. There are 37 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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