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| | <StructureSection load='3fcz' size='340' side='right'caption='[[3fcz]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='3fcz' size='340' side='right'caption='[[3fcz]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fcz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_14579 Atcc 14579]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FCZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fcz]] is a 2 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=3FCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FCZ FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.804Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2bc2|2bc2]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blm ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1396 ATCC 14579])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3fcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fcz OCA], [https://pdbe.org/3fcz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fcz RCSB], [https://www.ebi.ac.uk/pdbsum/3fcz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fcz ProSAT]</span></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=3fcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fcz OCA], [https://pdbe.org/3fcz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fcz RCSB], [https://www.ebi.ac.uk/pdbsum/3fcz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fcz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/BLA2_BACCE BLA2_BACCE]] Can hydrolyze carbapenem compounds.
| + | [https://www.uniprot.org/uniprot/BLA2_BACCE BLA2_BACCE] Can hydrolyze carbapenem compounds. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 14579]] | + | [[Category: Bacillus cereus]] |
| - | [[Category: Beta-lactamase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Carloni, P]] | + | [[Category: Carloni P]] |
| - | [[Category: Fabiane, S]] | + | [[Category: Fabiane S]] |
| - | [[Category: Simona, F]] | + | [[Category: Simona F]] |
| - | [[Category: Sutton, B]] | + | [[Category: Sutton B]] |
| - | [[Category: Tomatis, P]] | + | [[Category: Tomatis P]] |
| - | [[Category: Vila, A]] | + | [[Category: Vila A]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Metallo-beta-lactamase]]
| + | |
| - | [[Category: Zinc]]
| + | |
| Structural highlights
Function
BLA2_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 PubMed
Protein evolution is crucial for organismal adaptation and fitness. This process takes place by shaping a given 3-dimensional fold for its particular biochemical function within the metabolic requirements and constraints of the environment. The complex interplay between sequence, structure, functionality, and stability that gives rise to a particular phenotype has limited the identification of traits acquired through evolution. This is further complicated by the fact that mutations are pleiotropic, and interactions between mutations are not always understood. Antibiotic resistance mediated by beta-lactamases represents an evolutionary paradigm in which organismal fitness depends on the catalytic efficiency of a single enzyme. Based on this, we have dissected the structural and mechanistic features acquired by an optimized metallo-beta-lactamase (MbetaL) obtained by directed evolution. We show that antibiotic resistance mediated by this enzyme is driven by 2 mutations with sign epistasis. One mutation stabilizes a catalytically relevant intermediate by fine tuning the position of 1 metal ion; whereas the other acts by augmenting the protein flexibility. We found that enzyme evolution (and the associated antibiotic resistance) occurred at the expense of the protein stability, revealing that MbetaLs have not exhausted their stability threshold. Our results demonstrate that flexibility is an essential trait that can be acquired during evolution on stable protein scaffolds. Directed evolution aided by a thorough characterization of the selected proteins can be successfully used to predict future evolutionary events and design inhibitors with an evolutionary perspective.
Adaptive protein evolution grants organismal fitness by improving catalysis and flexibility.,Tomatis PE, Fabiane SM, Simona F, Carloni P, Sutton BJ, Vila AJ Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20605-10. Epub 2008 Dec 19. PMID:19098096[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tomatis PE, Fabiane SM, Simona F, Carloni P, Sutton BJ, Vila AJ. Adaptive protein evolution grants organismal fitness by improving catalysis and flexibility. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20605-10. Epub 2008 Dec 19. PMID:19098096 doi:0807989106
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