2v1z: Difference between revisions
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< | ==Structure of a TEM-1 beta-lactamase insertant allosterically regulated by kanamycin and anions.== | ||
<StructureSection load='2v1z' size='340' side='right'caption='[[2v1z]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2v1z]] 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=2V1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V1Z FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2v1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v1z OCA], [https://pdbe.org/2v1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v1z RCSB], [https://www.ebi.ac.uk/pdbsum/2v1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v1z ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v1/2v1z_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=2v1z ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Allosteric regulation of enzyme activity is a remarkable property of many biological catalysts. Up till now, engineering an allosteric regulation into native, unregulated enzymes has been achieved by the creation of hybrid proteins in which a natural receptor, whose conformation is controlled by ligand binding, is inserted into an enzyme structure. Here, we describe a monomeric enzyme, TEM1-beta-lactamase, that features an allosteric aminoglycoside binding site created de novo by directed-evolution methods. beta-Lactamases are highly efficient enzymes involved in the resistance of bacteria against beta-lactam antibiotics, such as penicillin. Aminoglycosides constitute another class of antibiotics that prevent bacterial protein synthesis, and are neither substrates nor ligands of the native beta-lactamases. Here we show that the engineered enzyme is regulated by the binding of kanamycin and other aminoglycosides. Kinetic and structural analyses indicate that the activation mechanism involves expulsion of an inhibitor that binds to an additional, fortuitous site on the engineered protein. These analyses also led to the defining of conditions that allowed an aminoglycoside to be detected at low concentration. | |||
Engineering an Allosteric Binding Site for Aminoglycosides into TEM1-beta-Lactamase.,Volkov AN, Barrios H, Mathonet P, Evrard C, Ubbink M, Declercq JP, Soumillion P, Fastrez J Chembiochem. 2011 Apr 11;12(6):904-13. doi: 10.1002/cbic.201000568. Epub, 2011 Mar 18. PMID:21425229<ref>PMID:21425229</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2v1z" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[ | |||
== | |||
< | |||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Barrios | [[Category: Large Structures]] | ||
[[Category: Declercq | [[Category: Barrios H]] | ||
[[Category: Evrard | [[Category: Declercq JP]] | ||
[[Category: Fastrez | [[Category: Evrard C]] | ||
[[Category: Mathonet | [[Category: Fastrez J]] | ||
[[Category: Soumillion | [[Category: Mathonet P]] | ||
[[Category: Soumillion P]] | |||
Latest revision as of 10:58, 23 October 2024
Structure of a TEM-1 beta-lactamase insertant allosterically regulated by kanamycin and anions.Structure of a TEM-1 beta-lactamase insertant allosterically regulated by kanamycin and anions.
Structural highlights
FunctionBLAT_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 PubMedAllosteric regulation of enzyme activity is a remarkable property of many biological catalysts. Up till now, engineering an allosteric regulation into native, unregulated enzymes has been achieved by the creation of hybrid proteins in which a natural receptor, whose conformation is controlled by ligand binding, is inserted into an enzyme structure. Here, we describe a monomeric enzyme, TEM1-beta-lactamase, that features an allosteric aminoglycoside binding site created de novo by directed-evolution methods. beta-Lactamases are highly efficient enzymes involved in the resistance of bacteria against beta-lactam antibiotics, such as penicillin. Aminoglycosides constitute another class of antibiotics that prevent bacterial protein synthesis, and are neither substrates nor ligands of the native beta-lactamases. Here we show that the engineered enzyme is regulated by the binding of kanamycin and other aminoglycosides. Kinetic and structural analyses indicate that the activation mechanism involves expulsion of an inhibitor that binds to an additional, fortuitous site on the engineered protein. These analyses also led to the defining of conditions that allowed an aminoglycoside to be detected at low concentration. Engineering an Allosteric Binding Site for Aminoglycosides into TEM1-beta-Lactamase.,Volkov AN, Barrios H, Mathonet P, Evrard C, Ubbink M, Declercq JP, Soumillion P, Fastrez J Chembiochem. 2011 Apr 11;12(6):904-13. doi: 10.1002/cbic.201000568. Epub, 2011 Mar 18. PMID:21425229[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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