6tj8
From Proteopedia
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==Escherichia coli transketolase in complex with cofactor analog 2'-methoxythiamine diphosphate== | ==Escherichia coli transketolase in complex with cofactor analog 2'-methoxythiamine diphosphate== | ||
| - | <StructureSection load='6tj8' size='340' side='right'caption='[[6tj8]]' scene=''> | + | <StructureSection load='6tj8' size='340' side='right'caption='[[6tj8]], [[Resolution|resolution]] 0.92Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TJ8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6tj8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TJ8 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tj8 OCA], [http://pdbe.org/6tj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tj8 RCSB], [http://www.ebi.ac.uk/pdbsum/6tj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tj8 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NDQ:2-[3-[(4-azanyl-2-methoxy-pyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-5-yl]ethyl+phosphono+hydrogen+phosphate'>NDQ</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tktA, tkt, b2935, JW5478 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transketolase Transketolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.2.1.1 2.2.1.1] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tj8 OCA], [http://pdbe.org/6tj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tj8 RCSB], [http://www.ebi.ac.uk/pdbsum/6tj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tj8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/TKT1_ECOLI TKT1_ECOLI]] Catalyzes the reversible transfer of a two-carbon ketol group from sedoheptulose-7-phosphate to glyceraldehyde-3-phosphate, producing xylulose-5-phosphate and ribose-5-phosphate. Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.<ref>PMID:17914867</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The natural antivitamin 2'-methoxy-thiamine (MTh) is implicated in the suppression of microbial growth. However, its mode of action and enzyme-selective inhibition mechanism have remained elusive. Intriguingly, MTh inhibits some thiamine diphosphate (ThDP) enzymes, while being coenzymatically active in others. Here we report the strong inhibition of Escherichia coli transketolase activity by MTh and unravel its mode of action and the structural basis thereof. The unique 2'-methoxy group of MTh diphosphate (MThDP) clashes with a canonical glutamate required for cofactor activation in ThDP-dependent enzymes. This glutamate is forced into a stable, anticatalytic low-barrier hydrogen bond with a neighboring glutamate, disrupting cofactor activation. Molecular dynamics simulations of transketolases and other ThDP enzymes identify active-site flexibility and the topology of the cofactor-binding locale as key determinants for enzyme-selective inhibition. Human enzymes either retain enzymatic activity with MThDP or preferentially bind authentic ThDP over MThDP, while core bacterial metabolic enzymes are inhibited, demonstrating therapeutic potential. | ||
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| + | Structural basis for antibiotic action of the B1 antivitamin 2'-methoxy-thiamine.,Rabe von Pappenheim F, Aldeghi M, Shome B, Begley T, de Groot BL, Tittmann K Nat Chem Biol. 2020 Aug 24. pii: 10.1038/s41589-020-0628-4. doi:, 10.1038/s41589-020-0628-4. PMID:32839604<ref>PMID:32839604</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6tj8" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Ecoli]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Transketolase]] |
| - | [[Category: Tittmann K]] | + | [[Category: Pappenheim, F Rabe von]] |
| + | [[Category: Tittmann, K]] | ||
| + | [[Category: Enzyme catalysis]] | ||
| + | [[Category: Pentose phosphate pathway]] | ||
| + | [[Category: Thiamin diphosphate]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 07:04, 2 September 2020
Escherichia coli transketolase in complex with cofactor analog 2'-methoxythiamine diphosphate
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