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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/Q7BNC2_ECOLX Q7BNC2_ECOLX] | | [https://www.uniprot.org/uniprot/Q7BNC2_ECOLX Q7BNC2_ECOLX] |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| 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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| <div class="pdbe-citations 3qnc" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |