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| | <StructureSection load='3zdj' size='340' side='right'caption='[[3zdj]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='3zdj' size='340' side='right'caption='[[3zdj]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zdj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZDJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zdj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZDJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4b88|4b88]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=3zdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdj OCA], [https://pdbe.org/3zdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zdj RCSB], [https://www.ebi.ac.uk/pdbsum/3zdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zdj 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=3zdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdj OCA], [https://pdbe.org/3zdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zdj RCSB], [https://www.ebi.ac.uk/pdbsum/3zdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zdj ProSAT]</span></td></tr> |
| | </table> | | </table> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Gavira, J A]] | + | [[Category: Gavira JA]] |
| - | [[Category: Risso, V A]] | + | [[Category: Risso VA]] |
| - | [[Category: Sanchez-Ruiz, J M]] | + | [[Category: Sanchez-Ruiz JM]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Hydrolase]]
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| Structural highlights
Publication Abstract from PubMed
We report a sequence reconstruction analysis targeting several Precambrian nodes in the evolution of class-A beta-lactamases and the preparation and experimental characterization of their encoded proteins. Despite extensive sequence differences with the modern enzymes ( approximately 100 amino acid differences), the proteins resurrected in the laboratory properly fold into the canonical lactamase structure. The encoded proteins from 2-3 billion years (Gyr)-old beta-lactamase sequences undergo cooperative two-state thermal denaturation and display very large denaturation temperature enhancements ( approximately 35 degrees C) relative to modern beta-lactamases. They degrade different antibiotics in vitro with catalytic efficiencies comparable to that of an average modern enzyme. This enhanced substrate promiscuity is not accompanied by significant changes in the active-site region as seen in static X-ray structures, suggesting a plausible role for dynamics in the evolution of function in these proteins. Laboratory resurrections of 2-3 Gyr-old beta-lactamases also endowed modern microorganisms with significant levels of resistance toward a variety of antibiotics, opening up the possibility of performing laboratory replays of the molecular tape of lactamase evolution. Overall, these results support the notions that Precambrian life was thermophilic and that proteins can evolve from substrate-promiscuous generalists into specialists during the course of natural evolution. They also highlight the biotechnological potential of laboratory resurrection of Precambrian proteins, as both high stability and enhanced promiscuity (likely contributors to high evolvability) are advantageous features in protein scaffolds for molecular design and laboratory evolution.
Hyperstability and Substrate Promiscuity in Laboratory Resurrections of Precambrian beta-Lactamases.,Risso VA, Gavira JA, Mejia-Carmona DF, Gaucher EA, Sanchez-Ruiz JM J Am Chem Soc. 2013 Feb 14. PMID:23394108[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Risso VA, Gavira JA, Mejia-Carmona DF, Gaucher EA, Sanchez-Ruiz JM. Hyperstability and Substrate Promiscuity in Laboratory Resurrections of Precambrian beta-Lactamases. J Am Chem Soc. 2013 Feb 14. PMID:23394108 doi:http://dx.doi.org/10.1021/ja311630a
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