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==Crystal structure of MbtI from Mycobacterium tuberculosis== | |||
<StructureSection load='3log' size='340' side='right'caption='[[3log]], [[Resolution|resolution]] 1.73Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3log]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LOG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LOG FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.73Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></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=3log FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3log OCA], [https://pdbe.org/3log PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3log RCSB], [https://www.ebi.ac.uk/pdbsum/3log PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3log ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MBTI_MYCTU MBTI_MYCTU] Mediates the production of salicylate from chorismate via an isochorismate intermediate. Presents both isochorismate synthase and isochorismate-pyruvate lyase activities. Salycilate is the starter unit in the production of the virulence-conferring salicylate-based siderophore mycobactin.<ref>PMID:16923875</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mycobacterium tuberculosis salicylate synthase (MbtI), a member of the chorismate-utilizing enzyme family, catalyses the first committed step in the biosynthesis of the siderophore mycobactin T. This complex secondary metabolite is essential for both virulence and survival of M. tuberculosis, the etiological agent of tuberculosis (TB). It is therefore anticipated that inhibitors of this enzyme may serve as TB therapies with a novel mode of action. Herein we describe the first inhibition study of M. tuberculosis MbtI using a library of functionalized benzoate-based inhibitors designed to mimic the substrate (chorismate) and intermediate (isochorismate) of the MbtI-catalyzed reaction. The most potent inhibitors prepared were those designed to mimic the enzyme intermediate, isochorismate. These compounds, based on a 2,3-dihydroxybenzoate scaffold, proved to be low-micromolar inhibitors of MbtI. The most potent inhibitors in this series possessed hydrophobic enol ether side chains at C3 in place of the enol-pyruvyl side chain found in chorismate and isochorismate. | |||
Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI).,Manos-Turvey A, Bulloch EM, Rutledge PJ, Baker EN, Lott JS, Payne RJ ChemMedChem. 2010 Jul 5;5(7):1067-79. PMID:20512795<ref>PMID:20512795</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3log" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Isochorismate pyruvate lyase|Isochorismate pyruvate lyase]] | *[[Isochorismate pyruvate lyase|Isochorismate pyruvate lyase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Baker | [[Category: Baker EN]] | ||
[[Category: Bulloch | [[Category: Bulloch EMM]] | ||
[[Category: Johnston | [[Category: Johnston JM]] | ||
[[Category: Lott | [[Category: Lott JS]] | ||
Latest revision as of 19:24, 1 November 2023
Crystal structure of MbtI from Mycobacterium tuberculosisCrystal structure of MbtI from Mycobacterium tuberculosis
Structural highlights
FunctionMBTI_MYCTU Mediates the production of salicylate from chorismate via an isochorismate intermediate. Presents both isochorismate synthase and isochorismate-pyruvate lyase activities. Salycilate is the starter unit in the production of the virulence-conferring salicylate-based siderophore mycobactin.[1] Publication Abstract from PubMedMycobacterium tuberculosis salicylate synthase (MbtI), a member of the chorismate-utilizing enzyme family, catalyses the first committed step in the biosynthesis of the siderophore mycobactin T. This complex secondary metabolite is essential for both virulence and survival of M. tuberculosis, the etiological agent of tuberculosis (TB). It is therefore anticipated that inhibitors of this enzyme may serve as TB therapies with a novel mode of action. Herein we describe the first inhibition study of M. tuberculosis MbtI using a library of functionalized benzoate-based inhibitors designed to mimic the substrate (chorismate) and intermediate (isochorismate) of the MbtI-catalyzed reaction. The most potent inhibitors prepared were those designed to mimic the enzyme intermediate, isochorismate. These compounds, based on a 2,3-dihydroxybenzoate scaffold, proved to be low-micromolar inhibitors of MbtI. The most potent inhibitors in this series possessed hydrophobic enol ether side chains at C3 in place of the enol-pyruvyl side chain found in chorismate and isochorismate. Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI).,Manos-Turvey A, Bulloch EM, Rutledge PJ, Baker EN, Lott JS, Payne RJ ChemMedChem. 2010 Jul 5;5(7):1067-79. PMID:20512795[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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