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| | ==X-ray crystal structure of OXA-23 A220 duplication clinical variant== | | ==X-ray crystal structure of OXA-23 A220 duplication clinical variant== |
| - | <StructureSection load='4k0w' size='340' side='right' caption='[[4k0w]], [[Resolution|resolution]] 1.20Å' scene=''> | + | <StructureSection load='4k0w' size='340' side='right'caption='[[4k0w]], [[Resolution|resolution]] 1.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k0w]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K0W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K0W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k0w]] 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=4K0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K0W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k0x|4k0x]]</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> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ari-1, bla(OXA-23), bla-OXA-23, blaOXA-146, blaOXA-23, OXA-23, oxa23 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=470 Acinetobacter baumannii])</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=4k0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k0w OCA], [https://pdbe.org/4k0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k0w RCSB], [https://www.ebi.ac.uk/pdbsum/4k0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k0w ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4k0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k0w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k0w RCSB], [http://www.ebi.ac.uk/pdbsum/4k0w PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/B6E129_ACIBA B6E129_ACIBA] |
| - | 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.
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| - | 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>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Beta-lactamase|Beta-lactamase]] | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Acinetobacter baumannii]] | | [[Category: Acinetobacter baumannii]] |
| - | [[Category: Beta-lactamase]] | + | [[Category: Large Structures]] |
| - | [[Category: Kaitany, K J]] | + | [[Category: Kaitany KJ]] |
| - | [[Category: Klinger, N V]] | + | [[Category: Klinger NV]] |
| - | [[Category: Leonard, D A]] | + | [[Category: Leonard DA]] |
| - | [[Category: Powers, R A]] | + | [[Category: Powers RA]] |
| - | [[Category: Carbapenemase]]
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| - | [[Category: Cephalosporinase]]
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| - | [[Category: Hydrolase]]
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