Hydroxylase - Revision history

Alexander Berchansky at 12:27, 19 January 2020

Alexander Berchansky — Sun, 19 Jan 2020 12:27:50 GMT

←Older revision		Revision as of 12:27, 19 January 2020
Line 9:		Line 9:
	Aromatic amino acid hydroxylases consists of phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase. 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>.		Aromatic amino acid hydroxylases consists of phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase. 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>.

-	'''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>.	+	'''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>.
	<br/>		<br/>
	See also [[Protein Stability and in Vivo Concentration of Missense Mutations in Phenylalanine Hydroxylase]].		See also [[Protein Stability and in Vivo Concentration of Missense Mutations in Phenylalanine Hydroxylase]].

Michal Harel at 09:45, 25 August 2019

Michal Harel — Sun, 25 Aug 2019 09:45:11 GMT

←Older revision		Revision as of 09:45, 25 August 2019
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	</StructureSection>		</StructureSection>
-	==3D structures of hydroxylases==

-	Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-	{{#tree:id=OrganizedByTopic\|openlevels=0\|
-	*Phenylalanine hydroxylase
-
-	**[[6n1k]] – hPAH (mutant) – human<br />
-	**[[6hyc]] – hPAH + cofactor<br />
-	**[[1j8t]], [[1pah]], [[2pah]] - hPAH catalytic domain<br />
-	**[[1tdw]] – hPAH catalytic domain (mutant) <br />
-	**[[6hpo]] – hPAH catalytic domain + Fe <br />
-	**[[3pah]], [[4pah]] – hPAH catalytic domain + adrenaline inhibitor<br />
-	**[[5pah]], [[6pah]] - hPAH catalytic domain + dopamine inhibitor<br />
-	**[[1j8u]] - hPAH catalytic domain + cofactor<br />
-	**[[1dmw]] - hPAH catalytic domain + cofactor<br />
-	**[[6hpo]] - hPAH catalytic domain + cofactor + Fe<br />
-	**[[1tg2]], [[1lrm]] - hPAH catalytic domain (mutant) + cofactor<br />
-	**[[1mmk]], [[1mmt]], [[1kw0]] - hPAH catalytic domain + cofactor + substrate<br />
-	**[[4anp]] - hPAH catalytic domain + pyrimidine derivative<br />
-	**[[5fii]], [[5fgi]] - hPAH residues 19-118 + phenylalanine<br />
-	**[[1phz]], [[2phm]], [[5den]], [[5fgj]], [[5den]] – rPAH - rat<br />
-	**[[5egq]] - rPAH (mutant) <br />
-	**[[5jk6]] - smPAH + Fe – slime mold<br />
-	**[[5jk5]] - smPAH + cofactor + Fe <br />
-	**[[5jk8]] - smPAH + cofactor + Fe + norleucine <br />
-	**[[2v27]], [[2v28]] – PAH – ''Colwellia psychrerythraea''<br />
-	**[[1ltu]], [[1ltv]] – CvPAH – ''Chromobacterium violaceum''<br />
-	**[[1phz]], [[2phm]], [[5fgj]], [[5den]] – rPAH - rat<br />
-	**[[5egq]] - rPAH (mutant) <br />
-	**[[4bpt]] – PAH –'' Legionella pneumophila''<br />
-	**[[1ltz]] - CvPAH + cofactor<br />
-	**[[3tcy]], [[3tk2]] – CvPAH + phenylalanine<br />
-	**[[3tk4]] – CvPAH + Co<br />
-	**[[4esm]], [[4etl]], [[4q3w]], [[4q3x]], [[4q3y]], [[4q3z]] - CvPAH (mutant) + Co<br />
-	**[[4jpx]] - CvPAH (mutant) + Co + phenylalanine<br />
-	**[[4jpy]] - CvPAH + Fe + phenylalanine<br />
-
-	*Tyrosine hydroxylase
-
-	**[[2xsn]] – hTH catalytic domain <br />
-	**[2toh]], [[1toh]] – TH catalytic and tetramerization domains - rat
-
-	*Tryptophan hydroxylase
-
-	**[[3hf8]], [[3hfb]], [[3hf6]], [[5tpg]], [[5l01]], [[5j6d]] – hTPH 1 catalytic domain+ inhibitor + Fe <br />
-	**[[1mlw]] – hTPH catalytic domain+ biopterin + Fe<br />
-	**[[4v06]] - hTPH 2 catalytic domain + Fe<br />
-	**[[3e2t]] – TPH 1 catalytic domain + Trp + Fe – chicken
-
-	*p-hydroxybenzoate hydroxylase
-
-	**[[1phh]] – PfPHBH + FAD + DHB – ''Pseudomonas fluorescens''<br />
-	**[[1dob]], [[1doc]], [[1pxa]], [[1pxb]], [[1pxc]] – PaPHBH + FAD + PHB – ''Pseudomonas aeruginosa''<br />
-	**[[2phh]] – PfPHBH + adenosine diphosphoribose + PHB <br />
-	**[[1pbb]] – PfPHBH + FAD + 2,4-DHB <br />
-	**[[1pbc]], [[1pbf]] – PfPHBH + FAD + 2-hydroxy-4-aminobenzoate <br />
-	**[[1pbd]] – PfPHBH + FAD + 4-aminobenzoate <br />
-	**[[1pbe]] – PfPHBH + FAD + PHB <br />
-	**[[1bkw]], [[1bf3]], [[1bgj]], [[1bgn]], [[1cc4]], [[1cc6]] – PfPHBH (mutant) + FAD + PHB <br />
-	**[[1pdh]] – PfPHBH + FAD derivative + PHB <br />
-	**[[1cj2]], [[1cj3]], [[1cj4]] – PfPHBH (mutant) + FAD derivative + PHB <br />
-	**[[1dod]], [[1doe]] – PaPHBH + FAD + 2,4-DHB <br />
-	**[[1ius]], [[1iut]], [[1iuu]] – PaPHBH + FAD + 4-aminobenzoate <br />
-	**[[1iuv]], [[1iuw]], [[1iux]] – PaPHBH + FAD + 4,4-DHB <br />
-	**[[1d7l]] – PaPHBH + FAD derivative + PHB <br />
-	**[[1k0i]], [[1ykj]] – PaPHBH (mutant) + FAD + PHB <br />
-	**[[1k0j]] – PaPHBH (mutant) + FAD + NADPH <br />
-	**[[1k0l]] – PaPHBH (mutant) + FAD <br />
-	**[[6dll]] – PfPHBH + FAD – ''Pseudomonas putida''<br />
-	**[[2dki]] – CtPHBH + FAD – ''Comamonas testosteroni''<br />
-	**[[2dkh]] – CtPHBH + FAD + hydroxy-benzoate <br />
-
-	*Apartyl/asparaginyl β-hydroxylase
-
-	**[[5jz6]] – hAAH oxygenase and TPR domain + malate + Mn <br />
-	**[[5apa]] – hAAH residues 562-758 + malate + Ni <br />
-	**[[5jza]] – hAAH oxygenase and TPR domain + oxalylglycine + Mn <br />
-	**[[5jz8]], [[5jzu]], [[6rk9]], [[5jqy]] – hAAH oxygenase and TPR domain + oxalylglycine + Mn + coagulation factor X peptide<br />
-	**[[5jtc]] – hAAH oxygenase and TPR domain + pyridine dicarboxylate + Mn + coagulation factor X peptide<br />
-
-	*Alpha-ketoglutarate-dependent L-arginine hydroxylase
-
-	**[[6dax]], [[6alm]], [[6aln]], [[6mp8]] – SvAAH + arginine + oxoglutarate + Fe – ''Streptomyces vinaceus''<br />
-	**[[6daz]], [[6alo]], [[6alp]], [[6alq]] – SvAAH + arginine + succinate + Fe <br />
-	**[[6db2]], [[6alr]] – SvAAH + homoarginine + succinate + V <br />
-	**[[6mp9]] – SvAAH + guanidinopentanoate + succinate + Fe <br />
-
-	*PLP-dependent L-arginine hydroxylase
-
-	**[[6c9b]] – SwAAH + PLP – ''Streptomyces wadayamensis''<br />
-	**[[5dj1]] – SwAAH + PLP + Mg<br />
-	**[[5dj3]] – SwAAH + PLP-arginine + Mg<br />
-	**[[5bk7]] – SwAAH (mutant) + PLP-arginine <br />
-	**[[6c8t]], [[6c92]] – SwAAH + PLP-arginine + PLP derivative<br />
-
-	*Leucine hydroxylase
-
-	**[[5nch]] – StAAH – ''Streptomyces'' <br />
-	**[[5nci]] – StAAH + leucine derivative + oxoglutarate + Co <br />
-	**[[5ncj]] – StAAH + leucine derivative + succinate + Mn <br />
-
-	*L-arginine b-hydroxylase or non-heme iron oxygenase
-
-	**[[4m23]] – SlORFP – ''Streptomyces lavendulae''<br />
-	**[[4m2i]] – SlORFP + Fe <br />
-	**[[4m25]] – SlORFP + Fe + ketoglutarate <br />
-	**[[4m27]], [[4m2c]] – SlORFP + Fe + Arg<br />
-	**[[4m2e]] – SlORFP + Fe + Arg derivative<br />
-	**[[4m2f]] – SlORFP + Fe + canavanine<br />
-	**[[4m2g]], [[4m26]] – SlORFP + Fe + succinate + Arg derivative<br />
-	**[[2wbo]] – SvVIOC + Fe + Arg – ''Streptomyces vinaceus''<br />
-	**[[2wbq]] – SvVIOC + Arg derivative<br />
-	**[[2wbp]] – SvVIOC + Fe + succinate + Arg derivative<br />
-
-	*Prolyl 4-hydroxylase
-
-	**[[4bt8]], [[2yq8]] - hPH a1 subunit collagen-binding domain<br />
-	**[[1tjc]] - hPH a1 subunit collagen-binding domain (mutant)<br />
-	**[[4btb]], [[4bta]], [[4bt9]] - hPH a1 subunit + peptide<br />
-	**[[6evl]] - hPH a2 subunit <br />
-	**[[6evm]], [[6evn]], [[6evo]], [[6evp]] - hPH a2 subunit + peptide<br />
-	**[[5hv0]] - PH + Cd – ''Bacillus anthracis'' <br />
-	**[[5c5u]] - PcvPH + Mn – Paramecium chlorella virus <br />
-	**[[5c5t]] - PcvPH + Mn + Zn <br />
-	**[[4p7x]] - RlPH + Co + pipecolic acid – ''Rhizobium loti'' <br />
-	**[[4p7w]] - RlPH + Co + proline<br />
-	**[[6iuq]] - PH + Fe – ''Phytophthora capsici''<br />
-	**[[6ey1]] - TaPH + Mn – ''Trichoplax adhaerens''<br />
-	**[[6f0w]] - TaPH + Mn + hypoxia inducible factor + oxalylglycine <br />
-	**[[2v4a]], [[2jij]] - CrPH – ''Chlamydomonas reinhardtii'' <br />
-	**[[2jig]] - CrPH + Zn + pyridine derivative<br />
-
-	*HIF prolyl hydroxylase 1 or egl nine homolog 2
-
-	**[[5v1b]] – hHPH-1 + Fe + inhibitor <br />
-
-	*HIF prolyl hydroxylase 2 or egl nine homolog 1
-
-	**[[5las]] – hHPH-2 + HIF <br />
-	**[[5l9b]] – hHPH-2 catalytic domain (mutant) + Mn + HIF + oxoglutarate <br />
-	**[[5l9v]], [[5la9]], [[3hqr]], [[3hqu]] – hHPH-2 catalytic domain (mutant) + Mn + HIF + oxalylglycine <br />
-	**[[5ox5]], [[5ox6]], [[4bqw]], [[4bqx]], [[4bqy]] – hHPH-2 catalytic domain + Mn + inhibitor <br />
-	**[[5l9r]] – hHPH-2 catalytic domain + Mn + oxalylglycine <br />
-	**[[5v18]], [[6nmq]], [[3ouh]], [[3oui]], [[3ouj]], [[2y34]], [[2hbt]], [[2hbu]], [[2g19]], [[2g1m]] – hHPH-2 catalytic domain + Fe + inhibitor <br />
-	**[[4jzr]] – hHPH-2 catalytic domain + Ni + inhibitor <br />
-	**[[2y33]] – hHPH-2 catalytic domain + Zn + inhibitor <br />
-	**[[5lat]], [[5lb6]], [[5lbb]], [[5lbc]], [[5lbe]], [[5lbf]], [[5a3u]], [[4uwd]], [[4kbz]] – hHPH-2 catalytic domain (mutant) + Mn + inhibitor <br />
-
-	*Lysine 4-hydroxylase
-
-	**[[6f9p]] – FlL4H + Fe – ''Flavobacterium'' <br />
-	**[[6exf]] – FlL4H + Fe + lysine <br />
-	**[[6euo]] – FlL4H + Fe + succinate derivative<br />
-	**[[6eur]] – FlL4H + Fe + oxoglutarate<br />
-	**[[6exh]] – FlL4H + Fe + lysine + succinate<br />
-
-	*Lysine 3-hydroxylase
-
-	**[[6f2e]] – CaL3H – ''Catenulispora acidiphila'' <br />
-	**[[6f2b]] – CaL3H + Fe + oxoglutarate <br />
-	**[[6f2a]] – CaL3H + Fe + lysine <br />
-	**[[6f6j]] – CaL3H + Fe + succinate + hydroxyl lysine <br />
-
-	*Salicilate hydroxylase
-
-	**[[5evy]] - PpSH + FAD + salicilate <br />
-
-	*Dopamine β-hydroxylase
-
-	**[[4zel]] - hDH + Cu <br />
-
-	*Ectoine hydroxylase
-
-	**[[4q5o]] - DH + Fe + 5-hydroxyectoine – ''Sphingopyxis alaskensis'' <br />
-
-	}}
	===Additional Resources===		===Additional Resources===
	For additional information, see: [[Amino Acid Synthesis & Metabolism]]		For additional information, see: [[Amino Acid Synthesis & Metabolism]]

Michal Harel at 09:43, 25 August 2019

Michal Harel — Sun, 25 Aug 2019 09:43:48 GMT

←Older revision		Revision as of 09:43, 25 August 2019
Line 41:		Line 41:

	Deficiency in tyrosine hydroxylase has been observed in dopa responsive dystonia and juvenile parkinsonism. A reduced 3,4-dihydroxyphenylalanine production is also observed in Parkinson’s disease<ref>PMID: 11849022</ref>.		Deficiency in tyrosine hydroxylase has been observed in dopa responsive dystonia and juvenile parkinsonism. A reduced 3,4-dihydroxyphenylalanine production is also observed in Parkinson’s disease<ref>PMID: 11849022</ref>.
		+
		+	==3D structures of hydroxylase==
		+	[[Hydroxylases 3D structures]]
		+
	</StructureSection>		</StructureSection>
	==3D structures of hydroxylases==		==3D structures of hydroxylases==
Line 48:		Line 52:
	*Phenylalanine hydroxylase		*Phenylalanine hydroxylase

-	**[[~~1tdw~~]] – hPAH (mutant) – human<br />	+	**[[6n1k]] – hPAH (mutant) – human<br />
		+	**[[6hyc]] – hPAH + cofactor<br />
	**[[1j8t]], [[1pah]], [[2pah]] - hPAH catalytic domain<br />		**[[1j8t]], [[1pah]], [[2pah]] - hPAH catalytic domain<br />
		+	**[[1tdw]] – hPAH catalytic domain (mutant) <br />
		+	**[[6hpo]] – hPAH catalytic domain + Fe <br />
	**[[3pah]], [[4pah]] – hPAH catalytic domain + adrenaline inhibitor<br />		**[[3pah]], [[4pah]] – hPAH catalytic domain + adrenaline inhibitor<br />
	**[[5pah]], [[6pah]] - hPAH catalytic domain + dopamine inhibitor<br />		**[[5pah]], [[6pah]] - hPAH catalytic domain + dopamine inhibitor<br />
	**[[1j8u]] - hPAH catalytic domain + cofactor<br />		**[[1j8u]] - hPAH catalytic domain + cofactor<br />
-	**[[1dmw]] - hPAH + cofactor<br />	+	**[[1dmw]] - hPAH catalytic domain + cofactor<br />
-	**[[1tg2]], [[1lrm]] - hPAH (mutant) + cofactor<br />	+	**[[6hpo]] - hPAH catalytic domain + cofactor + Fe<br />
		+	**[[1tg2]], [[1lrm]] - hPAH catalytic domain (mutant) + cofactor<br />
	**[[1mmk]], [[1mmt]], [[1kw0]] - hPAH catalytic domain + cofactor + substrate<br />		**[[1mmk]], [[1mmt]], [[1kw0]] - hPAH catalytic domain + cofactor + substrate<br />
	**[[4anp]] - hPAH catalytic domain + pyrimidine derivative<br />		**[[4anp]] - hPAH catalytic domain + pyrimidine derivative<br />
	**[[5fii]], [[5fgi]] - hPAH residues 19-118 + phenylalanine<br />		**[[5fii]], [[5fgi]] - hPAH residues 19-118 + phenylalanine<br />
		+	**[[1phz]], [[2phm]], [[5den]], [[5fgj]], [[5den]] – rPAH - rat<br />
		+	**[[5egq]] - rPAH (mutant) <br />
	**[[5jk6]] - smPAH + Fe – slime mold<br />		**[[5jk6]] - smPAH + Fe – slime mold<br />
	**[[5jk5]] - smPAH + cofactor + Fe <br />		**[[5jk5]] - smPAH + cofactor + Fe <br />
Line 105:		Line 115:
	**[[1k0l]] – PaPHBH (mutant) + FAD <br />		**[[1k0l]] – PaPHBH (mutant) + FAD <br />
	**[[6dll]] – PfPHBH + FAD – ''Pseudomonas putida''<br />		**[[6dll]] – PfPHBH + FAD – ''Pseudomonas putida''<br />
		+	**[[2dki]] – CtPHBH + FAD – ''Comamonas testosteroni''<br />
		+	**[[2dkh]] – CtPHBH + FAD + hydroxy-benzoate <br />

	*Apartyl/asparaginyl β-hydroxylase		*Apartyl/asparaginyl β-hydroxylase
Line 116:		Line 128:
	*Alpha-ketoglutarate-dependent L-arginine hydroxylase		*Alpha-ketoglutarate-dependent L-arginine hydroxylase

-	**[[6dax]], [[6alm]], [[6aln]] – SvAAH + arginine + oxoglutarate + Fe – ''Streptomyces vinaceus''<br />	+	**[[6dax]], [[6alm]], [[6aln]], [[6mp8]] – SvAAH + arginine + oxoglutarate + Fe – ''Streptomyces vinaceus''<br />
	**[[6daz]], [[6alo]], [[6alp]], [[6alq]] – SvAAH + arginine + succinate + Fe <br />		**[[6daz]], [[6alo]], [[6alp]], [[6alq]] – SvAAH + arginine + succinate + Fe <br />
	**[[6db2]], [[6alr]] – SvAAH + homoarginine + succinate + V <br />		**[[6db2]], [[6alr]] – SvAAH + homoarginine + succinate + V <br />
		+	**[[6mp9]] – SvAAH + guanidinopentanoate + succinate + Fe <br />

	*PLP-dependent L-arginine hydroxylase		*PLP-dependent L-arginine hydroxylase
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	**[[5dj1]] – SwAAH + PLP + Mg<br />		**[[5dj1]] – SwAAH + PLP + Mg<br />
	**[[5dj3]] – SwAAH + PLP-arginine + Mg<br />		**[[5dj3]] – SwAAH + PLP-arginine + Mg<br />
		+	**[[5bk7]] – SwAAH (mutant) + PLP-arginine <br />
		+	**[[6c8t]], [[6c92]] – SwAAH + PLP-arginine + PLP derivative<br />

	*Leucine hydroxylase		*Leucine hydroxylase
Line 131:		Line 146:
	**[[5nci]] – StAAH + leucine derivative + oxoglutarate + Co <br />		**[[5nci]] – StAAH + leucine derivative + oxoglutarate + Co <br />
	**[[5ncj]] – StAAH + leucine derivative + succinate + Mn <br />		**[[5ncj]] – StAAH + leucine derivative + succinate + Mn <br />
		+
		+	*L-arginine b-hydroxylase or non-heme iron oxygenase
		+
		+	**[[4m23]] – SlORFP – ''Streptomyces lavendulae''<br />
		+	**[[4m2i]] – SlORFP + Fe <br />
		+	**[[4m25]] – SlORFP + Fe + ketoglutarate <br />
		+	**[[4m27]], [[4m2c]] – SlORFP + Fe + Arg<br />
		+	**[[4m2e]] – SlORFP + Fe + Arg derivative<br />
		+	**[[4m2f]] – SlORFP + Fe + canavanine<br />
		+	**[[4m2g]], [[4m26]] – SlORFP + Fe + succinate + Arg derivative<br />
		+	**[[2wbo]] – SvVIOC + Fe + Arg – ''Streptomyces vinaceus''<br />
		+	**[[2wbq]] – SvVIOC + Arg derivative<br />
		+	**[[2wbp]] – SvVIOC + Fe + succinate + Arg derivative<br />

	*Prolyl 4-hydroxylase		*Prolyl 4-hydroxylase

		+	**[[4bt8]], [[2yq8]] - hPH a1 subunit collagen-binding domain<br />
		+	**[[1tjc]] - hPH a1 subunit collagen-binding domain (mutant)<br />
		+	**[[4btb]], [[4bta]], [[4bt9]] - hPH a1 subunit + peptide<br />
		+	**[[6evl]] - hPH a2 subunit <br />
		+	**[[6evm]], [[6evn]], [[6evo]], [[6evp]] - hPH a2 subunit + peptide<br />
	**[[5hv0]] - PH + Cd – ''Bacillus anthracis'' <br />		**[[5hv0]] - PH + Cd – ''Bacillus anthracis'' <br />
	**[[5c5u]] - PcvPH + Mn – Paramecium chlorella virus <br />		**[[5c5u]] - PcvPH + Mn – Paramecium chlorella virus <br />
Line 139:		Line 172:
	**[[4p7x]] - RlPH + Co + pipecolic acid – ''Rhizobium loti'' <br />		**[[4p7x]] - RlPH + Co + pipecolic acid – ''Rhizobium loti'' <br />
	**[[4p7w]] - RlPH + Co + proline<br />		**[[4p7w]] - RlPH + Co + proline<br />
		+	**[[6iuq]] - PH + Fe – ''Phytophthora capsici''<br />
		+	**[[6ey1]] - TaPH + Mn – ''Trichoplax adhaerens''<br />
		+	**[[6f0w]] - TaPH + Mn + hypoxia inducible factor + oxalylglycine <br />
		+	**[[2v4a]], [[2jij]] - CrPH – ''Chlamydomonas reinhardtii'' <br />
		+	**[[2jig]] - CrPH + Zn + pyridine derivative<br />
		+
		+	*HIF prolyl hydroxylase 1 or egl nine homolog 2
		+
		+	**[[5v1b]] – hHPH-1 + Fe + inhibitor <br />
		+
		+	*HIF prolyl hydroxylase 2 or egl nine homolog 1
		+
		+	**[[5las]] – hHPH-2 + HIF <br />
		+	**[[5l9b]] – hHPH-2 catalytic domain (mutant) + Mn + HIF + oxoglutarate <br />
		+	**[[5l9v]], [[5la9]], [[3hqr]], [[3hqu]] – hHPH-2 catalytic domain (mutant) + Mn + HIF + oxalylglycine <br />
		+	**[[5ox5]], [[5ox6]], [[4bqw]], [[4bqx]], [[4bqy]] – hHPH-2 catalytic domain + Mn + inhibitor <br />
		+	**[[5l9r]] – hHPH-2 catalytic domain + Mn + oxalylglycine <br />
		+	**[[5v18]], [[6nmq]], [[3ouh]], [[3oui]], [[3ouj]], [[2y34]], [[2hbt]], [[2hbu]], [[2g19]], [[2g1m]] – hHPH-2 catalytic domain + Fe + inhibitor <br />
		+	**[[4jzr]] – hHPH-2 catalytic domain + Ni + inhibitor <br />
		+	**[[2y33]] – hHPH-2 catalytic domain + Zn + inhibitor <br />
		+	**[[5lat]], [[5lb6]], [[5lbb]], [[5lbc]], [[5lbe]], [[5lbf]], [[5a3u]], [[4uwd]], [[4kbz]] – hHPH-2 catalytic domain (mutant) + Mn + inhibitor <br />
		+
		+	*Lysine 4-hydroxylase
		+
		+	**[[6f9p]] – FlL4H + Fe – ''Flavobacterium'' <br />
		+	**[[6exf]] – FlL4H + Fe + lysine <br />
		+	**[[6euo]] – FlL4H + Fe + succinate derivative<br />
		+	**[[6eur]] – FlL4H + Fe + oxoglutarate<br />
		+	**[[6exh]] – FlL4H + Fe + lysine + succinate<br />
		+
		+	*Lysine 3-hydroxylase
		+
		+	**[[6f2e]] – CaL3H – ''Catenulispora acidiphila'' <br />
		+	**[[6f2b]] – CaL3H + Fe + oxoglutarate <br />
		+	**[[6f2a]] – CaL3H + Fe + lysine <br />
		+	**[[6f6j]] – CaL3H + Fe + succinate + hydroxyl lysine <br />

	*Salicilate hydroxylase		*Salicilate hydroxylase

Michal Harel at 10:32, 21 August 2019

Michal Harel — Wed, 21 Aug 2019 10:32:09 GMT

←Older revision		Revision as of 10:32, 21 August 2019
Line 48:		Line 48:
	*Phenylalanine hydroxylase		*Phenylalanine hydroxylase

-	**[[2v27]], [[2v28]] – PAH – ''Colwellia psychrerythraea''<br />
-	**[[1ltu]], [[1ltv]] – CvPAH – ''Chromobacterium violaceum''<br />
-	**[[1phz]], [[2phm]], [[5fgj]], [[5den]] – rPAH - rat<br />
-	**[[5egq]] - rPAH (mutant) <br />
-	**[[4bpt]] – PAH –'' Legionella pneumophila''<br />
-	**[[1ltz]] - CvPAH + cofactor<br />
-	**[[3tcy]], [[3tk2]] – CvPAH + phenylalanine<br />
-	**[[3tk4]] – CvPAH + Co<br />
-	**[[4esm]], [[4etl]], [[4q3w]], [[4q3x]], [[4q3y]], [[4q3z]] - CvPAH (mutant) + Co<br />
-	**[[4jpx]] - CvPAH (mutant) + Co + phenylalanine<br />
-	**[[4jpy]] - CvPAH + Fe + phenylalanine<br />
	**[[1tdw]] – hPAH (mutant) – human<br />		**[[1tdw]] – hPAH (mutant) – human<br />
	**[[1j8t]], [[1pah]], [[2pah]] - hPAH catalytic domain<br />		**[[1j8t]], [[1pah]], [[2pah]] - hPAH catalytic domain<br />
Line 72:		Line 61:
	**[[5jk5]] - smPAH + cofactor + Fe <br />		**[[5jk5]] - smPAH + cofactor + Fe <br />
	**[[5jk8]] - smPAH + cofactor + Fe + norleucine <br />		**[[5jk8]] - smPAH + cofactor + Fe + norleucine <br />
		+	**[[2v27]], [[2v28]] – PAH – ''Colwellia psychrerythraea''<br />
		+	**[[1ltu]], [[1ltv]] – CvPAH – ''Chromobacterium violaceum''<br />
		+	**[[1phz]], [[2phm]], [[5fgj]], [[5den]] – rPAH - rat<br />
		+	**[[5egq]] - rPAH (mutant) <br />
		+	**[[4bpt]] – PAH –'' Legionella pneumophila''<br />
		+	**[[1ltz]] - CvPAH + cofactor<br />
		+	**[[3tcy]], [[3tk2]] – CvPAH + phenylalanine<br />
		+	**[[3tk4]] – CvPAH + Co<br />
		+	**[[4esm]], [[4etl]], [[4q3w]], [[4q3x]], [[4q3y]], [[4q3z]] - CvPAH (mutant) + Co<br />
		+	**[[4jpx]] - CvPAH (mutant) + Co + phenylalanine<br />
		+	**[[4jpy]] - CvPAH + Fe + phenylalanine<br />

	*Tyrosine hydroxylase		*Tyrosine hydroxylase

-	**[[2xsn]] – TH catalytic domain <br />	+	**[[2xsn]] – hTH catalytic domain <br />
	**[2toh]], [[1toh]] – TH catalytic and tetramerization domains - rat		**[2toh]], [[1toh]] – TH catalytic and tetramerization domains - rat

Joel L. Sussman at 16:17, 23 May 2019

Joel L. Sussman — Thu, 23 May 2019 16:17:48 GMT

←Older revision		Revision as of 16:17, 23 May 2019
Line 111:		Line 111:
	**[[5apa]] – hAAH residues 562-758 + malate + Ni <br />		**[[5apa]] – hAAH residues 562-758 + malate + Ni <br />
	**[[5jza]] – hAAH oxygenase and TPR domain + oxalylglycine + Mn <br />		**[[5jza]] – hAAH oxygenase and TPR domain + oxalylglycine + Mn <br />
-	**[[5jz8]], [[5jzu]], [[~~5jzz~~]], [[5jqy]] – hAAH oxygenase and TPR domain + oxalylglycine + Mn + coagulation factor X peptide<br />	+	**[[5jz8]], [[5jzu]], [[6rk9]], [[5jqy]] – hAAH oxygenase and TPR domain + oxalylglycine + Mn + coagulation factor X peptide<br />
	**[[5jtc]] – hAAH oxygenase and TPR domain + pyridine dicarboxylate + Mn + coagulation factor X peptide<br />		**[[5jtc]] – hAAH oxygenase and TPR domain + pyridine dicarboxylate + Mn + coagulation factor X peptide<br />

Alexander Berchansky at 13:00, 19 May 2019

Alexander Berchansky — Sun, 19 May 2019 13:00:25 GMT

←Older revision		Revision as of 13:00, 19 May 2019
Line 4:		Line 4:
	'''Hydroxylases''' are enzymes which add an hydroxyl group to organic compounds. This addition is the first step of aerobic oxidative degradation.		'''Hydroxylases''' are enzymes which add an hydroxyl group to organic compounds. This addition is the first step of aerobic oxidative degradation.

-	*<scene name='34/349251/Cv/2'>Secondary structure</scene> of Human phenylalanine hydroxylase catalytic domain (PDB entry [[1pah]]).	+	*<scene name='34/349251/Cv/4'>Secondary structure</scene> of Human phenylalanine hydroxylase catalytic domain (PDB entry [[1pah]]).
-	*<scene name='34/349251/Cv/3'>Fe+3 ion coordination site</scene> in Human phenylalanine hydroxylase catalytic domain (PDB entry [[1pah]]).	+	*<scene name='34/349251/Cv/5'>Fe+3 ion coordination site</scene> in Human phenylalanine hydroxylase catalytic domain (PDB entry [[1pah]]). Water molecules are shown as red spheres.

	Aromatic amino acid hydroxylases consists of phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase. 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>.		Aromatic amino acid hydroxylases consists of phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase. 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>.

Michal Harel at 10:45, 13 February 2019

Michal Harel — Wed, 13 Feb 2019 10:45:40 GMT

←Older revision		Revision as of 10:45, 13 February 2019
Line 24:		Line 24:

	<br/>		<br/>
-	~~For more details see [[Tryptophan hydroxylase 1 with bound tryptophan]].~~ TPH exists in two isoforms called TPH isoform 1 (TPH1) and TPH isoform 2 (TPH2)<ref name ="walther">PMID: 14563478</ref>. The existence of two isoforms was observed when TPH was purified and ~~characterised~~ from different tissues. The gene encoding for rabbit TPH1 was identified in 1987 by Grenett et al.<ref>PMID: 3475690</ref> and a few years later the human gene for TPH1 was identified on chromosome 11 <ref>PMID: 2055111</ref>. The gene for isoform 2 was identified in 2003 by Walther et al. and the human gene is located on chromosome 12 <ref>PMID: 12511643</ref>.	+	TPH exists in two isoforms called TPH isoform 1 (TPH1) and TPH isoform 2 (TPH2)<ref name ="walther">PMID: 14563478</ref>. The existence of two isoforms was observed when TPH was purified and characterized from different tissues. The gene encoding for rabbit TPH1 was identified in 1987 by Grenett et al.<ref>PMID: 3475690</ref> and a few years later the human gene for TPH1 was identified on chromosome 11 <ref>PMID: 2055111</ref>. The gene for isoform 2 was identified in 2003 by Walther et al. and the human gene is located on chromosome 12 <ref>PMID: 12511643</ref>.
	The two isoforms are expressed in different tissues. TPH2 is mainly expressed in serotonergic neurons of the brain and gut <ref name="Patel">PMID: 14960297</ref>. TPH1 is expressed in other parts of the body such as the pineal gland <ref name="Patel"/>, skin cells <ref>PMID: 14559114</ref>, mast cells<ref name="Levine"/>, intestinal mucosa and enterochromafin cells <ref>PMID: 3435461</ref> and in cancer cells <ref>PMID: 16654</ref>. The main difference between the two isoforms is that the N-terminal is extended by 46 residues in TPH2<ref name="walther"/>.		The two isoforms are expressed in different tissues. TPH2 is mainly expressed in serotonergic neurons of the brain and gut <ref name="Patel">PMID: 14960297</ref>. TPH1 is expressed in other parts of the body such as the pineal gland <ref name="Patel"/>, skin cells <ref>PMID: 14559114</ref>, mast cells<ref name="Levine"/>, intestinal mucosa and enterochromafin cells <ref>PMID: 3435461</ref> and in cancer cells <ref>PMID: 16654</ref>. The main difference between the two isoforms is that the N-terminal is extended by 46 residues in TPH2<ref name="walther"/>.
		+	For more details see [[Tryptophan hydroxylase 1 with bound tryptophan]].

	'''p-hydroxybenzoate hydroxylase''' (PHBH) is a flavoprotein involved in the degradation of aromatic compounds. PHBH catalyzes the conversion of p-hydroxybenzoate (PHB) and O<sub>2</sub> to dihydrobenzoate (DHB) and CO<sub>2</sub>. FAD is a co-factor of PHBH and NADPH is used as the reducing molecule in the reaction.		'''p-hydroxybenzoate hydroxylase''' (PHBH) is a flavoprotein involved in the degradation of aromatic compounds. PHBH catalyzes the conversion of p-hydroxybenzoate (PHB) and O<sub>2</sub> to dihydrobenzoate (DHB) and CO<sub>2</sub>. FAD is a co-factor of PHBH and NADPH is used as the reducing molecule in the reaction.

Michal Harel at 09:37, 18 July 2018

Michal Harel — Wed, 18 Jul 2018 09:37:59 GMT

←Older revision		Revision as of 09:37, 18 July 2018
Line 49:		Line 49:
	**[[2v27]], [[2v28]] – PAH – ''Colwellia psychrerythraea''<br />		**[[2v27]], [[2v28]] – PAH – ''Colwellia psychrerythraea''<br />
	**[[1ltu]], [[1ltv]] – CvPAH – ''Chromobacterium violaceum''<br />		**[[1ltu]], [[1ltv]] – CvPAH – ''Chromobacterium violaceum''<br />
-	**[[1phz]], [[2phm]] – rPAH - rat<br />	+	**[[1phz]], [[2phm]], [[5fgj]], [[5den]] – rPAH - rat<br />
	**[[5egq]] - rPAH (mutant) <br />		**[[5egq]] - rPAH (mutant) <br />
	**[[4bpt]] – PAH –'' Legionella pneumophila''<br />		**[[4bpt]] – PAH –'' Legionella pneumophila''<br />
Line 112:		Line 112:
	**[[5jz8]], [[5jzu]], [[5jzz]], [[5jqy]] – hAAH oxygenase and TPR domain + oxalylglycine + Mn + coagulation factor X peptide<br />		**[[5jz8]], [[5jzu]], [[5jzz]], [[5jqy]] – hAAH oxygenase and TPR domain + oxalylglycine + Mn + coagulation factor X peptide<br />
	**[[5jtc]] – hAAH oxygenase and TPR domain + pyridine dicarboxylate + Mn + coagulation factor X peptide<br />		**[[5jtc]] – hAAH oxygenase and TPR domain + pyridine dicarboxylate + Mn + coagulation factor X peptide<br />
		+
		+	*Alpha-ketoglutarate-dependent L-arginine hydroxylase
		+
		+	**[[6dax]], [[6alm]], [[6aln]] – SvAAH + arginine + oxoglutarate + Fe – ''Streptomyces vinaceus''<br />
		+	**[[6daz]], [[6alo]], [[6alp]], [[6alq]] – SvAAH + arginine + succinate + Fe <br />
		+	**[[6db2]], [[6alr]] – SvAAH + homoarginine + succinate + V <br />
		+
		+	*PLP-dependent L-arginine hydroxylase
		+
		+	**[[6c9b]] – SwAAH + PLP – ''Streptomyces wadayamensis''<br />
		+	**[[5dj1]] – SwAAH + PLP + Mg<br />
		+	**[[5dj3]] – SwAAH + PLP-arginine + Mg<br />
		+
		+	*Leucine hydroxylase
		+
		+	**[[5nch]] – StAAH – ''Streptomyces'' <br />
		+	**[[5nci]] – StAAH + leucine derivative + oxoglutarate + Co <br />
		+	**[[5ncj]] – StAAH + leucine derivative + succinate + Mn <br />

	*Prolyl 4-hydroxylase		*Prolyl 4-hydroxylase

Jaime Prilusky at 13:57, 14 June 2018

Jaime Prilusky — Thu, 14 Jun 2018 13:57:57 GMT

←Older revision		Revision as of 13:57, 14 June 2018
Line 103:		Line 103:
	**[[1k0j]] – PaPHBH (mutant) + FAD + NADPH <br />		**[[1k0j]] – PaPHBH (mutant) + FAD + NADPH <br />
	**[[1k0l]] – PaPHBH (mutant) + FAD <br />		**[[1k0l]] – PaPHBH (mutant) + FAD <br />
-	**[[~~5tti~~]] – PfPHBH + FAD – ''Pseudomonas putida''<br />	+	**[[6dll]] – PfPHBH + FAD – ''Pseudomonas putida''<br />

	*Apartyl/asparaginyl β-hydroxylase		*Apartyl/asparaginyl β-hydroxylase

Joel L. Sussman at 23:06, 14 January 2018

Joel L. Sussman — Sun, 14 Jan 2018 23:06:34 GMT

←Older revision		Revision as of 23:06, 14 January 2018
Line 2:		Line 2:
	== Function ==		== Function ==

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

	*<scene name='34/349251/Cv/2'>Secondary structure</scene> of Human phenylalanine hydroxylase catalytic domain (PDB entry [[1pah]]).		*<scene name='34/349251/Cv/2'>Secondary structure</scene> of Human phenylalanine hydroxylase catalytic domain (PDB entry [[1pah]]).