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| | ==The crystal structure of human 6 Pyruvoyl Tetrahydrobiopterin Synthase== | | ==The crystal structure of human 6 Pyruvoyl Tetrahydrobiopterin Synthase== |
| - | <StructureSection load='3i2b' size='340' side='right' caption='[[3i2b]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3i2b' size='340' side='right'caption='[[3i2b]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3i2b]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I2B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I2B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3i2b]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I2B FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gtq|1gtq]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3i2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i2b OCA], [https://pdbe.org/3i2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i2b RCSB], [https://www.ebi.ac.uk/pdbsum/3i2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i2b ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/6-pyruvoyltetrahydropterin_synthase 6-pyruvoyltetrahydropterin synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.12 4.2.3.12] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3i2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i2b OCA], [http://pdbe.org/3i2b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i2b RCSB], [http://www.ebi.ac.uk/pdbsum/3i2b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3i2b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PTPS_HUMAN PTPS_HUMAN]] Defects in PTS are the cause of BH4-deficient hyperphenylalaninemia type A (HPABH4A) [MIM:[http://omim.org/entry/261640 261640]]; also called 6-pyruvoyl-tetrahydropterin synthase deficiency (PTS deficiency) or hyperphenylalaninemia tetrahydrobiopterin-deficient due to PTS deficiency. HPABH4A is an autosomal recessive disorder characterized by depletion of the neurotransmitters dopamine and serotonin, and clinically by severe neurological symptoms unresponsive to the classic phenylalanine-low diet.<ref>PMID:10531334</ref> <ref>PMID:7698774</ref> <ref>PMID:8178819</ref> <ref>PMID:7493990</ref> <ref>PMID:8707300</ref> <ref>PMID:9222757</ref> <ref>PMID:9159737</ref> <ref>PMID:9450907</ref> <ref>PMID:10585341</ref> <ref>PMID:10220141</ref> <ref>PMID:10874306</ref> <ref>PMID:11388593</ref> | + | [https://www.uniprot.org/uniprot/PTPS_HUMAN PTPS_HUMAN] Defects in PTS are the cause of BH4-deficient hyperphenylalaninemia type A (HPABH4A) [MIM:[https://omim.org/entry/261640 261640]; also called 6-pyruvoyl-tetrahydropterin synthase deficiency (PTS deficiency) or hyperphenylalaninemia tetrahydrobiopterin-deficient due to PTS deficiency. HPABH4A is an autosomal recessive disorder characterized by depletion of the neurotransmitters dopamine and serotonin, and clinically by severe neurological symptoms unresponsive to the classic phenylalanine-low diet.<ref>PMID:10531334</ref> <ref>PMID:7698774</ref> <ref>PMID:8178819</ref> <ref>PMID:7493990</ref> <ref>PMID:8707300</ref> <ref>PMID:9222757</ref> <ref>PMID:9159737</ref> <ref>PMID:9450907</ref> <ref>PMID:10585341</ref> <ref>PMID:10220141</ref> <ref>PMID:10874306</ref> <ref>PMID:11388593</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTPS_HUMAN PTPS_HUMAN]] Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin. | + | [https://www.uniprot.org/uniprot/PTPS_HUMAN PTPS_HUMAN] Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i2/3i2b_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i2/3i2b_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 6-pyruvoyltetrahydropterin synthase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bountra, C]] | + | [[Category: Bountra C]] |
| - | [[Category: Bray, J E]] | + | [[Category: Bray JE]] |
| - | [[Category: Chaikuad, A]] | + | [[Category: Chaikuad A]] |
| - | [[Category: Cocking, R]] | + | [[Category: Cocking R]] |
| - | [[Category: Delft, F von]]
| + | [[Category: Edwards A]] |
| - | [[Category: Edwards, A]] | + | [[Category: Krojer T]] |
| - | [[Category: Krojer, T]] | + | [[Category: Muniz J]] |
| - | [[Category: Muniz, J]] | + | [[Category: Oppermann U]] |
| - | [[Category: Oppermann, U]] | + | [[Category: Pilka E]] |
| - | [[Category: Pilka, E]] | + | [[Category: Ugochukwu E]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Weigelt J]] |
| - | [[Category: Ugochukwu, E]] | + | [[Category: Yue WW]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Von Delft F]] |
| - | [[Category: Yue, W W]] | + | |
| - | [[Category: Pyruvoyl tetrahydrobiopterin synthase]] | + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Phenylketonuria]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Ptp synthase]]
| + | |
| - | [[Category: Pt]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Tetrahydrobiopterin biosynthesis]]
| + | |
| Structural highlights
Disease
PTPS_HUMAN Defects in PTS are the cause of BH4-deficient hyperphenylalaninemia type A (HPABH4A) [MIM:261640; also called 6-pyruvoyl-tetrahydropterin synthase deficiency (PTS deficiency) or hyperphenylalaninemia tetrahydrobiopterin-deficient due to PTS deficiency. HPABH4A is an autosomal recessive disorder characterized by depletion of the neurotransmitters dopamine and serotonin, and clinically by severe neurological symptoms unresponsive to the classic phenylalanine-low diet.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]
Function
PTPS_HUMAN Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Scherer-Oppliger T, Leimbacher W, Blau N, Thony B. Serine 19 of human 6-pyruvoyltetrahydropterin synthase is phosphorylated by cGMP protein kinase II. J Biol Chem. 1999 Oct 29;274(44):31341-8. PMID:10531334
- ↑ Ashida A, Owada M, Hatakeyama K. A missense mutation (A to G) of 6-pyruvoyltetrahydropterin synthase in tetrahydrobiopterin-deficient form of hyperphenylalaninemia. Genomics. 1994 Nov 15;24(2):408-10. PMID:7698774 doi:http://dx.doi.org/10.1006/geno.1994.1642
- ↑ Thony B, Leimbacher W, Blau N, Harvie A, Heizmann CW. Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase. Am J Hum Genet. 1994 May;54(5):782-92. PMID:8178819
- ↑ Oppliger T, Thony B, Nar H, Burgisser D, Huber R, Heizmann CW, Blau N. Structural and functional consequences of mutations in 6-pyruvoyltetrahydropterin synthase causing hyperphenylalaninemia in humans. Phosphorylation is a requirement for in vivo activity. J Biol Chem. 1995 Dec 8;270(49):29498-506. PMID:7493990
- ↑ Liu TT, Hsiao KJ. Identification of a common 6-pyruvoyl-tetrahydropterin synthase mutation at codon 87 in Chinese phenylketonuria caused by tetrahydrobiopterin synthesis deficiency. Hum Genet. 1996 Sep;98(3):313-6. PMID:8707300
- ↑ Oppliger T, Thony B, Kluge C, Matasovic A, Heizmann CW, Ponzone A, Spada M, Blau N. Identification of mutations causing 6-pyruvoyl-tetrahydropterin synthase deficiency in four Italian families. Hum Mutat. 1997;10(1):25-35. PMID:9222757 doi:<25::AID-HUMU4>3.0.CO;2-L 10.1002/(SICI)1098-1004(1997)10:1<25::AID-HUMU4>3.0.CO;2-L
- ↑ Hanihara T, Inoue K, Kawanishi C, Sugiyama N, Miyakawa T, Onishi H, Yamada Y, Osaka H, Kosaka K, Iwabuchi K, Owada M. 6-Pyruvoyl-tetrahydropterin synthase deficiency with generalized dystonia and diurnal fluctuation of symptoms: a clinical and molecular study. Mov Disord. 1997 May;12(3):408-11. PMID:9159737 doi:10.1002/mds.870120321
- ↑ Liu TT, Hsiao KJ, Lu SF, Wu SJ, Wu KF, Chiang SH, Liu XQ, Chen RG, Yu WM. Mutation analysis of the 6-pyruvoyl-tetrahydropterin synthase gene in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency. Hum Mutat. 1998;11(1):76-83. PMID:9450907 doi:<76::AID-HUMU12>3.0.CO;2-W 10.1002/(SICI)1098-1004(1998)11:1<76::AID-HUMU12>3.0.CO;2-W
- ↑ Romstad A, Guldberg P, Blau N, Guttler F. Single-step mutation scanning of the 6-pyruvoyltetrahydropterin synthase gene in patients with hyperphenylalaninemia. Clin Chem. 1999 Dec;45(12):2102-8. PMID:10585341
- ↑ Scherer-Oppliger T, Matasovic A, Laufs S, Levy HL, Quackenbush EJ, Blau N, Thony B. Dominant negative allele (N47D) in a compound heterozygote for a variant of 6-pyruvoyltetrahydropterin synthase deficiency causing transient hyperphenylalaninemia. Hum Mutat. 1999;13(4):286-9. PMID:10220141 doi:<286::AID-HUMU4>3.0.CO;2-C 10.1002/(SICI)1098-1004(1999)13:4<286::AID-HUMU4>3.0.CO;2-C
- ↑ Blau N, Scherer-Oppliger T, Baumer A, Riegel M, Matasovic A, Schinzel A, Jaeken J, Thony B. Isolated central form of tetrahydrobiopterin deficiency associated with hemizygosity on chromosome 11q and a mutant allele of PTPS. Hum Mutat. 2000;16(1):54-60. PMID:10874306 doi:<54::AID-HUMU10>3.0.CO;2-C 10.1002/1098-1004(200007)16:1<54::AID-HUMU10>3.0.CO;2-C
- ↑ Dudesek A, Roschinger W, Muntau AC, Seidel J, Leupold D, Thony B, Blau N. Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency. Eur J Pediatr. 2001 May;160(5):267-76. PMID:11388593
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