View source for 6pxx


==Class D beta-lactamase in complex with beta-lactam antibiotic==
<StructureSection load='6pxx' size='340' side='right'caption='[[6pxx]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pxx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PXX 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]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5R7:(2~{S},3~{R})-3-METHYL-2-[(2~{S},3~{R})-3-OXIDANYL-1-OXIDANYLIDENE-BUTAN-2-YL]-4-[(3~{S},5~{S})-5-[(SULFAMOYLAMINO)METHYL]PYRROLIDIN-3-YL]SULFANYL-3,4-DIHYDRO-2~{H}-PYRROLE-5-CARBOXYLIC+ACID'>5R7</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=6pxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pxx OCA], [https://pdbe.org/6pxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pxx RCSB], [https://www.ebi.ac.uk/pdbsum/6pxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pxx ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Carbapenem-resistant Enterobacteriaceae are a significant threat to public health, and a major resistance determinant that promotes this phenotype is the production of the OXA-48 carbapenemase. The activity of OXA-48 towards carbapenems is a puzzling phenotype as its hydrolytic activity against doripenem is non-detectable. To probe the mechanistic basis for this observation, we determined the 1.5 A resolution crystal structure of the deacylation deficient K73A variant of OXA-48 in complex with doripenem. Doripenem is observed in the Delta(1)R and Delta(1)S tautomeric states covalently attached to the catalytic S70 residue. Likely due to positioning of residue Y211, the carboxylate moiety of doripenem is making fewer hydrogen bonding/salt-bridge interactions with R250 compared to previously determined carbapenem OXA structures. Moreover, the hydroxyethyl side chain of doripenem is making van der Waals interactions with a key V120 residue, which likely affects the deacylation rate of doripenem. We hypothesize that positions V120 and Y211 play important roles in the carbapenemase profile of OXA-48. Herein, we provide insights for the further development of the carbapenem class of antibiotics that could render them less effective to hydrolysis by or even inhibit OXA carbapenemases.

Structural Analysis of The OXA-48 Carbapenemase Bound to A "Poor" Carbapenem Substrate, Doripenem.,Papp-Wallace KM, Kumar V, Zeiser ET, Becka SA, van den Akker F Antibiotics (Basel). 2019 Sep 11;8(3). pii: antibiotics8030145. doi:, 10.3390/antibiotics8030145. PMID:31514291<ref>PMID:31514291</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6pxx" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase 3D structures|ATPase 3D structures]]
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: Kumar V]]
[[Category: Van den Akker F]]