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| | ==Structure of Hydroxyethylthiazole kinase ThiM from Staphylococcus aureus in complex with substrate analog 2-(1,3,5-trimethyl-1H-pyrazole-4-yl)ethanol== | | ==Structure of Hydroxyethylthiazole kinase ThiM from Staphylococcus aureus in complex with substrate analog 2-(1,3,5-trimethyl-1H-pyrazole-4-yl)ethanol== |
| - | <StructureSection load='5cga' size='340' side='right' caption='[[5cga]], [[Resolution|resolution]] 1.87Å' scene=''> | + | <StructureSection load='5cga' size='340' side='right'caption='[[5cga]], [[Resolution|resolution]] 1.87Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5cga]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Staar Staar]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CGA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5cga]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_MRSA252 Staphylococcus aureus subsp. aureus MRSA252]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CGA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KP6:2-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)ETHANOL'>KP6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.87Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">thiM, SAR2181 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=282458 STAAR])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KP6:2-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)ETHANOL'>KP6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.50 2.7.1.50] </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=5cga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cga OCA], [https://pdbe.org/5cga PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cga RCSB], [https://www.ebi.ac.uk/pdbsum/5cga PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cga ProSAT]</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=5cga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cga OCA], [http://pdbe.org/5cga PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cga RCSB], [http://www.ebi.ac.uk/pdbsum/5cga PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cga ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/THIM_STAAR THIM_STAAR]] Catalyzes the phosphorylation of the hydroxyl group of 4-methyl-5-beta-hydroxyethylthiazole (THZ). | + | [https://www.uniprot.org/uniprot/THIM_STAAR THIM_STAAR] Catalyzes the phosphorylation of the hydroxyl group of 4-methyl-5-beta-hydroxyethylthiazole (THZ). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Staar]] | + | [[Category: Large Structures]] |
| - | [[Category: Transferase]] | + | [[Category: Staphylococcus aureus subsp. aureus MRSA252]] |
| - | [[Category: Betzel, C]] | + | [[Category: Betzel C]] |
| - | [[Category: Cang, H]] | + | [[Category: Cang H]] |
| - | [[Category: Drebes, J]] | + | [[Category: Drebes J]] |
| - | [[Category: Kuenz, M]] | + | [[Category: Kuenz M]] |
| - | [[Category: Windshuegel, B]] | + | [[Category: Windshuegel B]] |
| - | [[Category: Wrenger, C]] | + | [[Category: Wrenger C]] |
| - | [[Category: Bacterial thiamine biosynthesis]]
| + | |
| - | [[Category: Hydroxyethylthiazole kinase]]
| + | |
| - | [[Category: Substrate analog]]
| + | |
| Structural highlights
Function
THIM_STAAR Catalyzes the phosphorylation of the hydroxyl group of 4-methyl-5-beta-hydroxyethylthiazole (THZ).
Publication Abstract from PubMed
Infections caused by the methicillin-resistant Staphylococcus aureus (MRSA) are today known to be a substantial threat for global health. Emerging multi-drug resistant bacteria have created a substantial need to identify and discover new drug targets and to develop novel strategies to treat bacterial infections. A promising and so far untapped antibiotic target is the biosynthesis of vitamin B1 (thiamin). Thiamin in its activated form, thiamin pyrophosphate, is an essential co-factor for all organisms. Therefore, thiamin analogous compounds, when introduced into the vitamin B1 biosynthetic pathway and further converted into non-functional co-factors by the bacterium can function as pro-drugs which thus block various co-factor dependent pathways. We characterized one of the key enzymes within the S. aureus vitamin B1 biosynthetic pathway, 5-(hydroxyethyl)-4-methylthiazole kinase (SaThiM; EC 2.7.1.50), a potential target for pro-drug compounds and analyzed the native structure of SaThiM and complexes with the natural substrate 5-(hydroxyethyl)-4-methylthiazole (THZ) and two selected substrate analogues.
Structure of ThiM from Vitamin B1 biosynthetic pathway of Staphylococcus aureus - Insights into a novel pro-drug approach addressing MRSA infections.,Drebes J, Kunz M, Windshugel B, Kikhney AG, Muller IB, Eberle RJ, Oberthur D, Cang H, Svergun DI, Perbandt M, Betzel C, Wrenger C Sci Rep. 2016 Mar 10;6:22871. doi: 10.1038/srep22871. PMID:26960569[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Drebes J, Kunz M, Windshugel B, Kikhney AG, Muller IB, Eberle RJ, Oberthur D, Cang H, Svergun DI, Perbandt M, Betzel C, Wrenger C. Structure of ThiM from Vitamin B1 biosynthetic pathway of Staphylococcus aureus - Insights into a novel pro-drug approach addressing MRSA infections. Sci Rep. 2016 Mar 10;6:22871. doi: 10.1038/srep22871. PMID:26960569 doi:http://dx.doi.org/10.1038/srep22871
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