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==Crystal structure of G238A mutant of TEM-1 beta-lactamase in complex with a boronic acid inhibitor (sefb4)== | ==Crystal structure of G238A mutant of TEM-1 beta-lactamase in complex with a boronic acid inhibitor (sefb4)== | ||
<StructureSection load='1jwv' size='340' side='right' caption='[[1jwv]], [[Resolution|resolution]] 1.85Å' scene=''> | <StructureSection load='1jwv' size='340' side='right' caption='[[1jwv]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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='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=1jwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jwv OCA], [http://pdbe.org/1jwv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jwv RCSB], [http://www.ebi.ac.uk/pdbsum/1jwv PDBsum]</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=1jwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jwv OCA], [http://pdbe.org/1jwv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jwv RCSB], [http://www.ebi.ac.uk/pdbsum/1jwv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jwv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jw/1jwv_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jw/1jwv_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</div> | </div> | ||
<div class="pdbe-citations 1jwv" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1jwv" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 12:14, 17 January 2018
Crystal structure of G238A mutant of TEM-1 beta-lactamase in complex with a boronic acid inhibitor (sefb4)Crystal structure of G238A mutant of TEM-1 beta-lactamase in complex with a boronic acid inhibitor (sefb4)
Structural highlights
Function[BLAT_ECOLX] TEM-type are the most prevalent beta-lactamases in enterobacteria; they hydrolyze the beta-lactam bond in susceptible beta-lactam antibiotics, thus conferring resistance to penicillins and cephalosporins. TEM-3 and TEM-4 are capable of hydrolyzing cefotaxime and ceftazidime. TEM-5 is capable of hydrolyzing ceftazidime. TEM-6 is capable of hydrolyzing ceftazidime and aztreonam. TEM-8/CAZ-2, TEM-16/CAZ-7 and TEM-24/CAZ-6 are markedly active against ceftazidime. IRT-4 shows resistance to beta-lactamase inhibitors. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the beta-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182-->Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity. Evolution of an antibiotic resistance enzyme constrained by stability and activity trade-offs.,Wang X, Minasov G, Shoichet BK J Mol Biol. 2002 Jun 28;320(1):85-95. PMID:12079336[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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