3dwz: Difference between revisions
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==Meropenem Covalent Adduct with TB Beta-lactamase== | ==Meropenem Covalent Adduct with TB Beta-lactamase== | ||
<StructureSection load='3dwz' size='340' side='right' caption='[[3dwz]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='3dwz' size='340' side='right'caption='[[3dwz]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3dwz]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3dwz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DWZ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DWZ:(2S,3R,4S)-4-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-2-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-METHYL-3,4-DIHYDRO-2H-PYRROLE-5-CARBOXYLIC+ACID'>DWZ</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DWZ:(2S,3R,4S)-4-{[(3S,5S)-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL}-2-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-METHYL-3,4-DIHYDRO-2H-PYRROLE-5-CARBOXYLIC+ACID'>DWZ</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cg5|3cg5]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3cg5|3cg5]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaA, blaC ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaA, blaC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dwz OCA], [https://pdbe.org/3dwz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dwz RCSB], [https://www.ebi.ac.uk/pdbsum/3dwz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dwz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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</div> | </div> | ||
<div class="pdbe-citations 3dwz" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3dwz" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Large Structures]] | |||
[[Category: Blanchard, J S]] | [[Category: Blanchard, J S]] | ||
[[Category: Hugonnet, J E]] | [[Category: Hugonnet, J E]] | ||
Revision as of 10:05, 2 February 2022
Meropenem Covalent Adduct with TB Beta-lactamaseMeropenem Covalent Adduct with TB Beta-lactamase
Structural highlights
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 PubMedbeta-lactam antibiotics are ineffective against Mycobacterium tuberculosis, being rapidly hydrolyzed by the chromosomally encoded blaC gene product. The carbapenem class of beta-lactams are very poor substrates for BlaC, allowing us to determine the three-dimensional structure of the covalent BlaC-meropenem covalent complex at 1.8 angstrom resolution. When meropenem was combined with the beta-lactamase inhibitor clavulanate, potent activity against laboratory strains of M. tuberculosis was observed [minimum inhibitory concentration (MIC(meropenem)) less than 1 microgram per milliliter], and sterilization of aerobically grown cultures was observed within 14 days. In addition, this combination exhibited inhibitory activity against anaerobically grown cultures that mimic the "persistent" state and inhibited the growth of 13 extensively drug-resistant strains of M. tuberculosis at the same levels seen for drug-susceptible strains. Meropenem and clavulanate are Food and Drug Administration-approved drugs and could potentially be used to treat patients with currently untreatable disease. Meropenem-clavulanate is effective against extensively drug-resistant Mycobacterium tuberculosis.,Hugonnet JE, Tremblay LW, Boshoff HI, Barry CE 3rd, Blanchard JS Science. 2009 Feb 27;323(5918):1215-8. PMID:19251630[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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