2nxa: Difference between revisions
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< | ==Structure of Zn-dependent Metallo-Beta-Lactamase from Bacillus Cereus R121H, C221D Double Mutant== | ||
<StructureSection load='2nxa' size='340' side='right'caption='[[2nxa]], [[Resolution|resolution]] 2.29Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2nxa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_cereus Bacillus cereus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NXA FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.29Å</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=2nxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nxa OCA], [https://pdbe.org/2nxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nxa RCSB], [https://www.ebi.ac.uk/pdbsum/2nxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nxa ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BLA2_BACCE BLA2_BACCE] Can hydrolyze carbapenem compounds. | |||
== 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/nx/2nxa_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2nxa ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Metallo-beta-lactamases (MbetaLs) are bacterial Zn(II)-dependent hydrolases that confer broad-spectrum resistance to beta-lactam antibiotics. These enzymes can be subdivided into three subclasses (B1, B2 and B3) that differ in their metal binding sites and their characteristic tertiary structure. To date there are no clinically useful pan-MbetaL inhibitors available, mainly due to the unawareness of key catalytic features common to all MbetaL brands. Here we have designed, expressed and characterized two double mutants of BcII, a di-Zn(II) B1-MbetaL from Bacillus cereus, namely BcII-R121H/C221D (BcII-HD) and BcII-R121H/C221S (BcII-HS). These mutants display modified environments at the so-called Zn2 site or DCH site, reproducing the metal coordination environments of structurally related metallohydrolases. Through a combination of structural and functional studies, we found that BcII-HD is an impaired beta-lactamase even as a di-Zn(II) enzyme, whereas BcII-HS exhibits the ability to exist as mono or di-Zn(II) species in solution, with different catalytic performances. We show that these effects result from an altered position of Zn2, which is incapable of providing a productive interaction with the substrate beta-lactam ring. These results indicate that the position of Zn2 is essential for a productive substrate binding and hydrolysis. | |||
The Zn2 position in metallo-beta-lactamases is critical for activity: a study on chimeric metal sites on a conserved protein scaffold.,Gonzalez JM, Medrano Martin FJ, Costello AL, Tierney DL, Vila AJ J Mol Biol. 2007 Nov 9;373(5):1141-56. Epub 2007 Aug 21. PMID:17915249<ref>PMID:17915249</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2nxa" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Bacillus cereus]] | [[Category: Bacillus cereus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Gonzalez JM]] | ||
[[Category: Medrano Martin FJ]] | |||
[[Category: Vila AJ]] | |||
Latest revision as of 13:25, 30 August 2023
Structure of Zn-dependent Metallo-Beta-Lactamase from Bacillus Cereus R121H, C221D Double MutantStructure of Zn-dependent Metallo-Beta-Lactamase from Bacillus Cereus R121H, C221D Double Mutant
Structural highlights
FunctionBLA2_BACCE Can hydrolyze carbapenem compounds. 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 PubMedMetallo-beta-lactamases (MbetaLs) are bacterial Zn(II)-dependent hydrolases that confer broad-spectrum resistance to beta-lactam antibiotics. These enzymes can be subdivided into three subclasses (B1, B2 and B3) that differ in their metal binding sites and their characteristic tertiary structure. To date there are no clinically useful pan-MbetaL inhibitors available, mainly due to the unawareness of key catalytic features common to all MbetaL brands. Here we have designed, expressed and characterized two double mutants of BcII, a di-Zn(II) B1-MbetaL from Bacillus cereus, namely BcII-R121H/C221D (BcII-HD) and BcII-R121H/C221S (BcII-HS). These mutants display modified environments at the so-called Zn2 site or DCH site, reproducing the metal coordination environments of structurally related metallohydrolases. Through a combination of structural and functional studies, we found that BcII-HD is an impaired beta-lactamase even as a di-Zn(II) enzyme, whereas BcII-HS exhibits the ability to exist as mono or di-Zn(II) species in solution, with different catalytic performances. We show that these effects result from an altered position of Zn2, which is incapable of providing a productive interaction with the substrate beta-lactam ring. These results indicate that the position of Zn2 is essential for a productive substrate binding and hydrolysis. The Zn2 position in metallo-beta-lactamases is critical for activity: a study on chimeric metal sites on a conserved protein scaffold.,Gonzalez JM, Medrano Martin FJ, Costello AL, Tierney DL, Vila AJ J Mol Biol. 2007 Nov 9;373(5):1141-56. Epub 2007 Aug 21. PMID:17915249[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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