View source for 6rzr


==Structure of IMP-13 metallo-beta-lactamase complexed with hydrolysed imipenem==
<StructureSection load='6rzr' size='340' side='right'caption='[[6rzr]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rzr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RZR 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8YF:(2R)-2-[(2S,3R)-1,3-bis(oxidanyl)-1-oxidanylidene-butan-2-yl]-4-(2-methanimidamidoethylsulfanyl)-2,3-dihydro-1H-pyrrole+-5-carboxylic+acid'>8YF</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6rzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rzr OCA], [https://pdbe.org/6rzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rzr RCSB], [https://www.ebi.ac.uk/pdbsum/6rzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rzr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q7WYA8_PSEAI Q7WYA8_PSEAI] 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rzr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Kolonko M]]
[[Category: Popowicz GM]]
[[Category: Sattler M]]
[[Category: Softley C]]
[[Category: Zak KM]]