View source for 7rpc


==X-ray crystal structure of OXA-24/40 K84D in complex with ertapenem==
<StructureSection load='7rpc' size='340' side='right'caption='[[7rpc]], [[Resolution|resolution]] 2.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7rpc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RPC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6H7:(1S,4R,5S,6S)-3-{[(3S,5S)-5-carbamoylpyrrolidin-3-yl]sulfanyl}-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic+acid'>6H7</scene>, <scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<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'>[https://proteopedia.org/fgij/fg.htm?mol=7rpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rpc OCA], [https://pdbe.org/7rpc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rpc RCSB], [https://www.ebi.ac.uk/pdbsum/7rpc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rpc ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The evolution of multidrug resistance (MDR) in Acinetobacter spp. increases the risk of our best antibiotics losing their efficacy. From a clinical perspective, the carbapenem-hydrolyzing class D beta-lactamase (CHDL) subfamily present in Acetinobacter spp. is particularly concerning due to its ability to confer resistance to carbapenems. The kinetic profiles of class D beta-lactamases exhibit variability in carbapenem hydrolysis, suggesting functional differences. To better understand the structure-function relationship between the CHDL OXA-24/40 found in A. baumannii and carbapenem substrates, we analyzed steady-state kinetics with the carbapenem antibiotics meropenem and ertapenem, and determined the structures of complexes of OXA-24/40 bound to imipenem, meropenem, doripenem, and ertapenem, as well as the expanded-spectrum cephalosporin cefotaxime, using X-ray crystallography. We show that OXA-24/40 exhibits a preference for ertapenem compared to meropenem, imipenem, and doripenem, with an increase in catalytic efficiency of up to four-fold. We suggest that superposition of the nine OXA-24/40 complexes will better inform future inhibitor design efforts by providing insight into the complicated and varying ways in which carbapenems are selected and bound by class D beta-lactamases.

Conformational flexibility in carbapenem hydrolysis drives substrate specificity of the class D carbapenemase OXA-24/40.,Mitchell JM, June CM, Baggett VL, Lowe BC, Ruble JF, Bonomo RA, Leonard DA, Powers RA J Biol Chem. 2022 Jun 13:102127. doi: 10.1016/j.jbc.2022.102127. PMID:35709986<ref>PMID:35709986</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7rpc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Beta-lactamase]]
[[Category: Large Structures]]
[[Category: June, C M]]
[[Category: Mitchell, J M]]
[[Category: Powers, R A]]
[[Category: Carbapenem]]
[[Category: Carbapenemase]]
[[Category: Hydrolase]]
[[Category: Hydrolase-inhibitor complex]]