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| | <StructureSection load='1ig3' size='340' side='right'caption='[[1ig3]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1ig3' size='340' side='right'caption='[[1ig3]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ig3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1IG3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ig3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IG3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IG3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VIB:3-(4-AMINO-2-METHYL-PYRIMIDIN-5-YLMETHYL)-5-(2-HYDROXY-ETHYL)-4-METHYL-THIAZOL-3-IUM'>VIB</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VIB:3-(4-AMINO-2-METHYL-PYRIMIDIN-5-YLMETHYL)-5-(2-HYDROXY-ETHYL)-4-METHYL-THIAZOL-3-IUM'>VIB</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thiamine_diphosphokinase Thiamine diphosphokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.2 2.7.6.2] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thiamine_diphosphokinase Thiamine diphosphokinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.6.2 2.7.6.2] </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=1ig3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ig3 OCA], [http://pdbe.org/1ig3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ig3 RCSB], [http://www.ebi.ac.uk/pdbsum/1ig3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ig3 ProSAT]</span></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=1ig3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ig3 OCA], [https://pdbe.org/1ig3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ig3 RCSB], [https://www.ebi.ac.uk/pdbsum/1ig3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ig3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TPK1_MOUSE TPK1_MOUSE]] Catalyzes the phosphorylation of thiamine to thiamine pyrophosphate. Can also catalyze the phosphorylation of pyrithiamine to pyrithiamine pyrophosphate.<ref>PMID:10567383</ref> <ref>PMID:16365036</ref> | + | [[https://www.uniprot.org/uniprot/TPK1_MOUSE TPK1_MOUSE]] Catalyzes the phosphorylation of thiamine to thiamine pyrophosphate. Can also catalyze the phosphorylation of pyrithiamine to pyrithiamine pyrophosphate.<ref>PMID:10567383</ref> <ref>PMID:16365036</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Structural highlights
Function
[TPK1_MOUSE] Catalyzes the phosphorylation of thiamine to thiamine pyrophosphate. Can also catalyze the phosphorylation of pyrithiamine to pyrithiamine pyrophosphate.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Thiamin pyrophosphate (TPP) is a coenzyme derived from vitamin B1 (thiamin). TPP synthesis in eukaryotes requires thiamin pyrophosphokinase (TPK), which catalyzes the transfer of a pyrophosphate group from ATP to thiamin. TPP is essential for central metabolic processes, including the formation of acetyl CoA from glucose and the Krebs cycle. Deficiencies in human thiamin metabolism result in beriberi and Wernicke encephalopathy. The crystal structure of mouse TPK was determined by multiwavelength anomalous diffraction at 2.4 A resolution, and the structure of TPK complexed with thiamin has been refined at 1.9 A resolution. The TPK polypeptide folds as an alpha/beta-domain and a beta-sandwich domain, which share a central ten-stranded mixed beta-sheet. TPK subunits associate as a dimer, and thiamin is bound in the dimer interface. Despite lacking apparent sequence homology with other proteins, the alpha/beta-domain resembles the Rossman fold and is similar to other kinase structures, including another pyrophosphokinase and a thiamin biosynthetic enzyme. Comparison of mouse and yeast TPK structures reveals differences that could be exploited in developing species-specific inhibitors of potential use as antimicrobial agents.
Crystal structure of thiamin pyrophosphokinase.,Timm DE, Liu J, Baker LJ, Harris RA J Mol Biol. 2001 Jun 29;310(1):195-204. PMID:11419946[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nosaka K, Onozuka M, Nishino H, Nishimura H, Kawasaki Y, Ueyama H. Molecular cloning and expression of a mouse thiamin pyrophosphokinase cDNA. J Biol Chem. 1999 Nov 26;274(48):34129-33. PMID:10567383
- ↑ Liu JY, Timm DE, Hurley TD. Pyrithiamine as a substrate for thiamine pyrophosphokinase. J Biol Chem. 2006 Mar 10;281(10):6601-7. Epub 2005 Dec 19. PMID:16365036 doi:10.1074/jbc.M510951200
- ↑ Timm DE, Liu J, Baker LJ, Harris RA. Crystal structure of thiamin pyrophosphokinase. J Mol Biol. 2001 Jun 29;310(1):195-204. PMID:11419946 doi:10.1006/jmbi.2001.4727
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