3i2b: Difference between revisions

Latest revision as of 15:55, 1 November 2023

The crystal structure of human 6 Pyruvoyl Tetrahydrobiopterin Synthase

Structural highlights

3i2b is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	EDO, MG, NI, PEG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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:https://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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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:https://dx.doi.org/10.1006/geno.1994.1642

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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

[8] 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

[9] 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

[10] 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

[11] 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

[12] 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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@@ Line 1: / Line 1: @@
-[[Image:3i2b.png|left|200px]]
-<!--
+==The crystal structure of human 6 Pyruvoyl Tetrahydrobiopterin Synthase==
-The line below this paragraph, containing "STRUCTURE_3i2b", creates the "Structure Box" on the page.
+<StructureSection load='3i2b' size='340' side='right'caption='[[3i2b]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<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>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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>
-{{STRUCTURE_3i2b|  PDB=3i2b  |  SCENE=  }}
+<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>
+</table>
-===The crystal structure of human 6 Pyruvoyl Tetrahydrobiopterin Synthase===
+== Disease ==
+[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 ==
-==About this Structure==
+[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.
-[[3i2b]] is a 12 chain structure with sequence from [http://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].
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
-==See Also==
+Check<jmol>
-*[[Urate Oxidase]]
+  <jmolCheckbox>
-[[Category: 6-pyruvoyltetrahydropterin synthase]]
+    <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>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3i2b ConSurf].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Large Structures]]
-[[Category: Bountra, C.]]
+[[Category: Arrowsmith CH]]
-[[Category: Bray, J E.]]
+[[Category: Bountra C]]
-[[Category: Chaikuad, A.]]
+[[Category: Bray JE]]
-[[Category: Cocking, R.]]
+[[Category: Chaikuad A]]
-[[Category: Delft, F von.]]
+[[Category: Cocking R]]
-[[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: SGC, Structural Genomics Consortium.]]
+[[Category: Ugochukwu E]]
-[[Category: Ugochukwu, E.]]
+[[Category: Weigelt J]]
-[[Category: Weigelt, J.]]
+[[Category: Yue WW]]
-[[Category: Yue, W W.]]
+[[Category: Von Delft F]]
-[[Category: 6 pyruvoyl tetrahydrobiopterin synthase]]
-[[Category: Disease mutation]]
-[[Category: Lyase]]
-[[Category: Metal-binding]]
-[[Category: Phenylketonuria]]
-[[Category: Phosphoprotein]]
-[[Category: Ptp synthase]]
-[[Category: Pt]]
-[[Category: Sgc]]
-[[Category: Structural genomic]]
-[[Category: Structural genomics consortium]]
-[[Category: Tetrahydrobiopterin biosynthesis]]
-[[Category: Zinc]]

3i2b: Difference between revisions

Latest revision as of 15:55, 1 November 2023

The crystal structure of human 6 Pyruvoyl Tetrahydrobiopterin Synthase

Structural highlights

Disease

Function

Evolutionary Conservation

References

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