View source for 6uvk


==OXA-48 bound by inhibitor CDD-97==
<StructureSection load='6uvk' size='340' side='right'caption='[[6uvk]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6uvk]] is a 4 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=6UVK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UVK 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=QHY:1-{4-[4-(2-ethoxyphenyl)piperazin-1-yl]-1,3,5-triazin-2-yl}piperidine-4-carboxylic+acid'>QHY</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=6uvk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uvk OCA], [https://pdbe.org/6uvk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uvk RCSB], [https://www.ebi.ac.uk/pdbsum/6uvk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uvk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bacterial resistance to beta-lactam antibiotics is largely mediated by beta-lactamases, which catalyze the hydrolysis of these drugs and continue to emerge in response to antibiotic use. beta-Lactamases that hydrolyze the last resort carbapenem class of beta-lactam antibiotics (carbapenemases) are a growing global health threat. Inhibitors have been developed to prevent beta-lactamase-mediated hydrolysis and restore the efficacy of these antibiotics. However, there are few inhibitors available for problematic carbapenemases such as oxacillinase-48 (OXA-48). A DNA-encoded chemical library approach was used to rapidly screen for compounds that bind and potentially inhibit OXA-48. Using this approach, a hit compound, CDD-97, was identified with submicromolar potency (Ki = 0.53 +/- 0.08 muM) against OXA-48. X-ray crystallography showed that CDD-97 binds noncovalently in the active site of OXA-48. Synthesis and testing of derivatives of CDD-97 revealed structure-activity relationships and informed the design of a compound with a 2-fold increase in potency. CDD-97, however, synergizes poorly with beta-lactam antibiotics to inhibit the growth of bacteria expressing OXA-48 due to poor accumulation into E. coli. Despite the low in vivo activity, CDD-97 provides new insights into OXA-48 inhibition and demonstrates the potential of using DNA-encoded chemistry technology to rapidly identify beta-lactamase binders and to study beta-lactamase inhibition, leading to clinically useful inhibitors.

Identifying Oxacillinase-48 Carbapenemase Inhibitors Using DNA-Encoded Chemical Libraries.,Taylor DM, Anglin J, Park S, Ucisik MN, Faver JC, Simmons N, Jin Z, Palaniappan M, Nyshadham P, Li F, Campbell J, Hu L, Sankaran B, Prasad BVV, Huang H, Matzuk MM, Palzkill T ACS Infect Dis. 2020 Mar 25. doi: 10.1021/acsinfecdis.0c00015. PMID:32182432<ref>PMID:32182432</ref>

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

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: Hu L]]
[[Category: Palzkill TG]]
[[Category: Prasad BVV]]
[[Category: Sankaran B]]
[[Category: Taylor DM]]