3qnc: Difference between revisions
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==Crystal Structure of a Rationally Designed OXA-10 Variant Showing Carbapenemase Activity, OXA-10loop48== | |||
<StructureSection load='3qnc' size='340' side='right' caption='[[3qnc]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3qnc]] is a 2 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=3QNC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QNC FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO2:CARBON+DIOXIDE'>CO2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qnb|3qnb]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaOXA-10(loop48) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=668369 Escherichia coli DH5[alpha]])</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=3qnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qnc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qnc RCSB], [http://www.ebi.ac.uk/pdbsum/3qnc PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Benvenuti, M | [[Category: Benvenuti, M]] | ||
[[Category: Carboni, F | [[Category: Carboni, F]] | ||
[[Category: Docquier, J D | [[Category: Docquier, J D]] | ||
[[Category: Luca, F De | [[Category: Luca, F De]] | ||
[[Category: Mangani, S | [[Category: Mangani, S]] | ||
[[Category: Pozzi, C | [[Category: Pozzi, C]] | ||
[[Category: Rossolini, G M | [[Category: Rossolini, G M]] | ||
[[Category: Antibiotic resistance]] | [[Category: Antibiotic resistance]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Hydrolysis of amide bond of beta-lactam compound]] | [[Category: Hydrolysis of amide bond of beta-lactam compound]] | ||
Revision as of 10:46, 19 December 2014
Crystal Structure of a Rationally Designed OXA-10 Variant Showing Carbapenemase Activity, OXA-10loop48
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