4k0w

</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=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>

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== 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

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