Hydroxylase

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[[Image:2pah-b.jpg|left |300 px]]
[[Image:2pah-b.jpg|left |300 px]]
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== Function ==
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The enzyme family of aromatic amino acid hydroxylases consists of '''[[phenylalanine hydroxylase]]''' (PAH), '''[[tyrosine hydroxylase]]''' (TH) and '''[[tryptophan hydroxylase]]''' ([[TPH]]).
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Hydroxylases are enzymes which add an hydroxyl group to organic compounds. This addition is the first step of aerobic oxidative degradation.
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These enzymes all contain iron and use BH<sub>4</sub> as a co-substrate in the hydroxylation of their respective aromatic amino acids. Additionally all mammalian AAAH form homotetramers and each monomer consists of three domains. These domains are the N-terminal regulatory domain (100-150 residues), the catalytic domain (approximately 315 residues) and the C-terminal tetramerisation domain (approximately 30-40 residues)<ref>PMID: 10800597</ref>.
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Aromatic amino acid hydroxylases consists of phenylalanine hydroxylase, '''[[tyrosine hydroxylase]]''' (TH) and '''[[tryptophan hydroxylase]]''' ([[TPH]]). These enzymes all contain iron and use BH<sub>4</sub> as a co-substrate in the hydroxylation of their respective aromatic amino acids. Additionally all mammalian AAAH form homotetramers and each monomer consists of three domains. These domains are the N-terminal regulatory domain (100-150 residues), the catalytic domain (approximately 315 residues) and the C-terminal tetramerization domain (approximately 30-40 residues)<ref>PMID: 10800597</ref>.
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'''Phenylalanine hydroxylase''' (PAH) is found in the liver where it catalyses the hydroxylation of phenylalanine to tyrosine. This is the first step in the oxidative degradation of phenylalanine<ref>PMID: 13428782</ref>. Mutations in PAH leading to a decrease in enzyme activity result in the disease phenylketonuria, where phenylalanine is converted to phenylpyruvate. Phenylpyruvate is toxic and leads to mental retardation. PAH is also found in some bacteria, but only PAH from the bacteria ''Chromobacterium violaceum''<ref>PMID: 9748224</ref> and ''Colwellia psychrerythraea''<ref>PMID: 17537732</ref> have been characterized. The bacterial PAHs are monomeric and do not contain a regulatory domain. All the [[aromatic amino acid hydroxylases]] are believed to have evolved from common ancestor containing only the catalytic domain<ref>PMID: 3475690</ref>.
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{{STRUCTURE_2pah | PDB=2pah | SCENE= }}
{{STRUCTURE_2pah | PDB=2pah | SCENE= }}
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==3D structures of Aromatic amino acid hydroxylases==
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==3D structures of hydroxylases==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*Phenylalanine hydroxylase
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**[[2v27]], [[2v28]] – PAH – ''Colwellia psychrerythraea''<br />
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**[[1ltu]], [[1ltv]] – CvPAH – ''Chromobacterium violaceum''<br />
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**[[1phz]], [[2phm]] – PAH - rat<br />
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**[[4bpt]] – PAH –'' Legionella pneumophila''<br />
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**[[1ltz]] - CvPAH + cofactor<br />
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**[[3tcy]], [[3tk2]] – CvPAH + phenylalanine<br />
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**[[3tk4]] – CvPAH + Co<br />
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**[[4esm]], [[4etl]], [[4q3w]], [[4q3x]], [[4q3y]], [[4q3z]] - CvPAH (mutant) + Co<br />
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**[[4jpx]] - CvPAH (mutant) + Co + phenylalanine<br />
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**[[4jpy]] - CvPAH + Fe + phenylalanine<br />
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**[[1tdw]] – hPAH (mutant) – human<br />
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**[[1j8t]], [[1pah]], [[2pah]] - hPAH catalytic domain<br />
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**[[3pah]], [[4pah]] – hPAH catalytic domain + adrenaline inhibitor<br />
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**[[5pah]], [[6pah]] - hPAH catalytic domain + dopamine inhibitor<br />
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**[[1j8u]] - hPAH catalytic domain + cofactor<br />
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**[[1dmw]] - hPAH + cofactor<br />
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**[[1tg2]], [[1lrm]] - hPAH (mutant) + cofactor<br />
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**[[1mmk]], [[1mmt]], [[1kw0]] - hPAH catalytic domain + cofactor + substrate<br />
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**[[4anp]] - hPAH catalytic domain + pyrimidine derivative
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[[Phenylalanine hydroxylase]]
 
[[Tyrosine hydroxylase]]
[[Tyrosine hydroxylase]]
[[Tryptophan hydroxylase]]
[[Tryptophan hydroxylase]]
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}}
===Additional Resources===
===Additional Resources===
For additional information, see: [[Amino Acid Synthesis & Metabolism]]
For additional information, see: [[Amino Acid Synthesis & Metabolism]]

Revision as of 07:35, 28 January 2016

Image:2pah-b.jpg

Contents

Function

Hydroxylases are enzymes which add an hydroxyl group to organic compounds. This addition is the first step of aerobic oxidative degradation.

Aromatic amino acid hydroxylases consists of phenylalanine hydroxylase, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH). These enzymes all contain iron and use BH4 as a co-substrate in the hydroxylation of their respective aromatic amino acids. Additionally all mammalian AAAH form homotetramers and each monomer consists of three domains. These domains are the N-terminal regulatory domain (100-150 residues), the catalytic domain (approximately 315 residues) and the C-terminal tetramerization domain (approximately 30-40 residues)[1].

Phenylalanine hydroxylase (PAH) is found in the liver where it catalyses the hydroxylation of phenylalanine to tyrosine. This is the first step in the oxidative degradation of phenylalanine[2]. Mutations in PAH leading to a decrease in enzyme activity result in the disease phenylketonuria, where phenylalanine is converted to phenylpyruvate. Phenylpyruvate is toxic and leads to mental retardation. PAH is also found in some bacteria, but only PAH from the bacteria Chromobacterium violaceum[3] and Colwellia psychrerythraea[4] have been characterized. The bacterial PAHs are monomeric and do not contain a regulatory domain. All the aromatic amino acid hydroxylases are believed to have evolved from common ancestor containing only the catalytic domain[5].


Template:STRUCTURE 2pah

3D structures of hydroxylases

Updated on 28-January-2016


Tyrosine hydroxylase

Tryptophan hydroxylase

Additional Resources

For additional information, see: Amino Acid Synthesis & Metabolism

References

  1. ↑ Fitzpatrick PF. The aromatic amino acid hydroxylases. Adv Enzymol Relat Areas Mol Biol. 2000;74:235-94. PMID:10800597
  2. ↑ KAUFMAN S. The enzymatic conversion of phenylalanine to tyrosine. J Biol Chem. 1957 May;226(1):511-24. PMID:13428782
  3. ↑ Chen D, Frey PA. Phenylalanine hydroxylase from Chromobacterium violaceum. Uncoupled oxidation of tetrahydropterin and the role of iron in hyroxylation. J Biol Chem. 1998 Oct 2;273(40):25594-601. PMID:9748224
  4. ↑ 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. 2007 Jul 27;282(30):21973-86. Epub 2007 May 30. PMID:17537732 doi:10.1074/jbc.M610174200
  5. ↑ 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. 1987 Aug;84(16):5530-4. PMID:3475690
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