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6r73
From Proteopedia
(Difference between revisions)
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<StructureSection load='6r73' size='340' side='right'caption='[[6r73]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='6r73' size='340' side='right'caption='[[6r73]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6r73]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R73 OCA]. For a <b>guided tour on the structure components</b> use [http:// | + | <table><tr><td colspan='2'>[[6r73]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R73 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6R73 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMP:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-BIS(OXIDANYL)-1-OXIDANYLIDENE-BUTAN-2-YL]-4-[(3~{S},5~{S})-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL-3-METHYL-3,4-DIHYDRO-2~{H}-PYRROLE-5-CARBOXYLIC+ACID'>LMP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMP:(2~{S},3~{R},4~{S})-2-[(2~{S},3~{R})-1,3-BIS(OXIDANYL)-1-OXIDANYLIDENE-BUTAN-2-YL]-4-[(3~{S},5~{S})-5-(DIMETHYLCARBAMOYL)PYRROLIDIN-3-YL]SULFANYL-3-METHYL-3,4-DIHYDRO-2~{H}-PYRROLE-5-CARBOXYLIC+ACID'>LMP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla-imp13, bla-IMP13, blaIMP-13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://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'>[http:// | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6r73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r73 OCA], [http://pdbe.org/6r73 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r73 RCSB], [http://www.ebi.ac.uk/pdbsum/6r73 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r73 ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Multi-drug resistance among Gram-negative bacteria is a major global public health threat. Metallo-beta-lactamases (MBLs) target the most widely-used antibiotic class, the beta-lactams, including the most recent-generation carbapenems. Interspecies spread renders these enzymes a serious clinical threat and there are no clinically-available inhibitors. We present crystal structures of IMP-13, a structurally-uncharacterized MBL from Gram-negative Pseudomonas aerugionasa found in clinical outbreaks globally, and characterize the binding using solution NMR-spectroscopy and molecular-dynamics simulations. Crystal structures of apo IMP-13 and bound to four clinically-relevant carbapenem antibiotics (doripenem, ertapenem, imipenem and meropenem) are presented. Active site plasticity and the active-site loop, where a tryptophan residue stabilizes the antibiotic core scaffold, are essential to the substrate-binding mechanism. The conserved carbapenem scaffold plays the most significant role in IMP-13 binding, explaining the broad substrate specificity. The observed plasticity and substrate-locking mechanism provide opportunities for rational drug design of novel metallo-beta-lactamase inhibitors, essential in the fight against antibiotic resistance. | ||
| + | |||
| + | Structure and molecular recognition mechanism of IMP-13 metallo-beta-lactamase.,Softley CA, Zak KM, Bostock MJ, Fino R, Zhou RX, Kolonko M, Mejdi-Nitiu R, Meyer H, Sattler M, Popowicz GM Antimicrob Agents Chemother. 2020 Mar 23. pii: AAC.00123-20. doi:, 10.1128/AAC.00123-20. PMID:32205343<ref>PMID:32205343</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6r73" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 07:04, 29 April 2020
Structure of IMP-13 metallo-beta-lactamase complexed with hydrolysed meropenem
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