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'''Unreleased structure'''


The entry 4k0x is ON HOLD
==X-ray Crystal Structure of OXA-23 from Acinetobacter baumannii==
<StructureSection load='4k0x' size='340' side='right'caption='[[4k0x]], [[Resolution|resolution]] 1.61&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4k0x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K0X 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]] 1.61&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</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=4k0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k0x OCA], [https://pdbe.org/4k0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k0x RCSB], [https://www.ebi.ac.uk/pdbsum/4k0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k0x ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLO23_ACIBA BLO23_ACIBA] Class D beta-lactamase which confers resistance to the beta-lactam antibiotics, including ampicillin, and carbapenems such as imipenem and meropenem (PubMed:18725452, PubMed:20194701, PubMed:24012371, PubMed:30530607, PubMed:35420470). Acts via hydrolysis of the beta-lactam ring (PubMed:23877677, PubMed:24012371, PubMed:30530607, PubMed:35420470). Has penicillin-, cephalosporin- and carbapenem-hydrolyzing activities, but lacks ceftazidime-hydrolyzing activity (PubMed:23877677, PubMed:24012371, PubMed:30530607, PubMed:35420470).<ref>PMID:18725452</ref> <ref>PMID:20194701</ref> <ref>PMID:23877677</ref> <ref>PMID:24012371</ref> <ref>PMID:30530607</ref> <ref>PMID:35420470</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Class D beta-lactamases that hydrolyze carbapenems such as imipenem and doripenem are a recognized danger to the efficacy of these "last resort" beta-lactam antibiotics. Like all known class D carbapenemases, OXA-23 cannot hydrolyze the expanded-spectrum cephalosporin, ceftazidime. OXA-146 is an OXA-23 subfamily clinical variant that differs from the parent enzyme by a single alanine (A220) inserted in the loop connecting beta-strands beta5 and beta6. We discovered that this insertion enables OXA-146 to bind and hydrolyze ceftazidime with efficiency comparable to other extended-spectrum class D beta-lactamases. OXA-146 also binds and hydrolyzes aztreonam, cefotaxime, ceftriaxone and ampicillin with higher efficiency than OXA-23, and preserves activity against doripenem. In this study, we report the X-ray crystal structures of both the OXA-23 and OXA-146 enzymes at 1.6 A and 1.2 A resolution. A comparison of the two structures shows that the extra alanine moves a methionine (M221) out of its normal position where it forms a bridge over the top of the active site. This single amino acid insertion also lengthens the beta5-beta6 loop, moving the entire backbone of this region further away from the active site. A model of ceftazidime bound in the active site reveals that these two structural alterations are both likely to relieve steric clashes between the bulky R1 side-chain of ceftazidime and OXA-23. With activity against all four classes of beta-lactam antibiotics, OXA-146 represents an alarming new threat to the treatment of infections caused by Acinetobacter spp.


Authors: Klinger, N.V., Ramey, M.E., Leonard, D.A., Powers, R.A.
STRUCTURES OF THE CLASS D CARBAPENEMASES OXA-23 AND OXA-146: MECHANISTIC BASIS OF ACTIVITY AGAINST CARBAPENEMS, EXTENDED-SPECTRUM CEPHALOSPORINS AND AZTREONAM.,Kaitany KC, Klinger NV, June CM, Ramey ME, Bonomo RA, Powers RA, Leonard DA Antimicrob Agents Chemother. 2013 Jul 22. PMID:23877677<ref>PMID:23877677</ref>


Description: X-ray Crystal Structure of OXA-23 from Acinetobacter baumannii
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4k0x" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acinetobacter baumannii]]
[[Category: Large Structures]]
[[Category: Klinger NV]]
[[Category: Leonard DA]]
[[Category: Powers RA]]
[[Category: Ramey ME]]
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