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| | ==Crystal Structure of an Engineered OXA-10 Variant with Carbapenemase Activity, OXA-10loop24== | | ==Crystal Structure of an Engineered OXA-10 Variant with Carbapenemase Activity, OXA-10loop24== |
| - | <StructureSection load='3qnb' size='340' side='right' caption='[[3qnb]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='3qnb' size='340' side='right'caption='[[3qnb]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qnb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_dh5[alpha] Escherichia coli dh5[alpha]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QNB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QNB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qnb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_DH5alpha Escherichia coli DH5alpha]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QNB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.95Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qnc|3qnc]]</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=3qnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qnb OCA], [https://pdbe.org/3qnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qnb RCSB], [https://www.ebi.ac.uk/pdbsum/3qnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qnb ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaOXA-10(loop24) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=668369 Escherichia coli DH5[alpha]])</td></tr>
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| - | <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>
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| - | <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=3qnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qnb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qnb RCSB], [http://www.ebi.ac.uk/pdbsum/3qnb PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q7BNC2_ECOLX Q7BNC2_ECOLX] |
| - | Class D beta-lactamases with carbapenemase activity are emerging as carbapenem-resistance determinants in gram-negative bacterial pathogens, mostly Acinetobacter baumannii and Klebsiella pneumoniae. Carbapenemase activity is an unusual feature among class D beta-lactamases, and the structural elements responsible for this activity remain unclear. Based on structural and molecular dynamics data, we previously hypothesized a potential role of the residues located in the short-loop connecting strands beta5 and beta6 (the beta5-beta6 loop) in conferring the carbapenemase activity of the OXA-48 enzyme. In this work, the narrow-spectrum OXA-10 class D beta-lactamase, which is unable to hydrolyze carbapenems, was used as a model to investigate the possibility of evolving carbapenemase activity by replacement of the beta5-beta6 loop with those present in three different lineages of class D carbapenemases (OXA-23, OXA-24, and OXA-48). Biological assays and kinetic measurements showed that all three OXA-10-derived hybrids acquired significant carbapenemase activity. Structural analysis of the OXA-10loop24 and OXA-10loop48 hybrids revealed no significant changes in the molecular fold of the enzyme, except for the orientation of the substituted beta5-beta6 loops, which was reminiscent of that found in their parental enzymes. These results demonstrate the crucial role of the beta5-beta6 loop in the carbapenemase activity of class D beta-lactamases, and provide previously unexplored insights into the mechanism by which these enzymes can evolve carbapenemase activity.
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| - | Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D beta-lactamase OXA-10 by rational protein design.,De Luca F, Benvenuti M, Carboni F, Pozzi C, Rossolini GM, Mangani S, Docquier JD Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18424-9. Epub 2011 Oct 31. PMID:22042844<ref>PMID:22042844</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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| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Large Structures]] |
| - | [[Category: Benvenuti, M]] | + | [[Category: Benvenuti M]] |
| - | [[Category: Carboni, F]] | + | [[Category: Carboni F]] |
| - | [[Category: Docquier, J D]] | + | [[Category: De Luca F]] |
| - | [[Category: Luca, F De]] | + | [[Category: Docquier JD]] |
| - | [[Category: Mangani, S]] | + | [[Category: Mangani S]] |
| - | [[Category: Pozzi, C]] | + | [[Category: Pozzi C]] |
| - | [[Category: Rossolini, G M]] | + | [[Category: Rossolini GM]] |
| - | [[Category: Antibiotic resistance]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Hydrolysis of amide bond of beta-lactam compound]]
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