1jwz

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[[Image:1jwz.jpg|left|200px]]
 
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{{Structure
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==Crystal structure of TEM-64 beta-lactamase in complex with a boronic acid inhibitor (105)==
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|PDB= 1jwz |SIZE=350|CAPTION= <scene name='initialview01'>1jwz</scene>, resolution 1.80&Aring;
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<StructureSection load='1jwz' size='340' side='right'caption='[[1jwz]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=105:N-[5-METHYL-3-O-TOLYL-ISOXAZOLE-4-CARBOXYLIC ACID AMIDE] BORONIC ACID'>105</scene>
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<table><tr><td colspan='2'>[[1jwz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JWZ FirstGlance]. <br>
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|ACTIVITY= [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]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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|GENE= bla ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=105:N-[5-METHYL-3-O-TOLYL-ISOXAZOLE-4-CARBOXYLIC+ACID+AMIDE]+BORONIC+ACID'>105</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jwz OCA], [https://pdbe.org/1jwz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jwz RCSB], [https://www.ebi.ac.uk/pdbsum/1jwz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jwz ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BLAT_ECOLX 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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jw/1jwz_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1jwz ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Pressured 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--&gt;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.
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'''Crystal structure of TEM-64 beta-lactamase in complex with a boronic acid inhibitor (105)'''
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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<ref>PMID:12079336</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1jwz" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Pressured 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--&gt;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.
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*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1JWZ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JWZ OCA].
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__TOC__
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</StructureSection>
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12079336 12079336]
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[[Category: Beta-lactamase]]
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[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Minasov, G.]]
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[[Category: Minasov G]]
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[[Category: Shoichet, B K.]]
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[[Category: Shoichet BK]]
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[[Category: Wang, X.]]
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[[Category: Wang X]]
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[[Category: 105]]
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[[Category: antibiotic resistance]]
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[[Category: beta-lactamase]]
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[[Category: crystal structure]]
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[[Category: evolution]]
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[[Category: serine hydrolase]]
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[[Category: tem-64]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:09:38 2008''
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Current revision

Crystal structure of TEM-64 beta-lactamase in complex with a boronic acid inhibitor (105)

PDB ID 1jwz

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