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| | <StructureSection load='5zft' size='340' side='right'caption='[[5zft]], [[Resolution|resolution]] 1.93Å' scene=''> | | <StructureSection load='5zft' size='340' side='right'caption='[[5zft]], [[Resolution|resolution]] 1.93Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zft]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"clostridium_licheniforme"_weigmann_1898 "clostridium licheniforme" weigmann 1898]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZFT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ZFT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zft]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZFT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CED:5-METHYL-2-[2-OXO-1-(2-THIOPHEN-2-YL-ACETYLAMINO)-ETHYL]-3,6-DIHYDRO-2H-[1,3]THIAZINE-4-CARBOXYLIC+ACID'>CED</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]] 1.93Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">penP, blaP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1402 "Clostridium licheniforme" Weigmann 1898])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CED:5-METHYL-2-[2-OXO-1-(2-THIOPHEN-2-YL-ACETYLAMINO)-ETHYL]-3,6-DIHYDRO-2H-[1,3]THIAZINE-4-CARBOXYLIC+ACID'>CED</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=5zft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zft OCA], [https://pdbe.org/5zft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zft RCSB], [https://www.ebi.ac.uk/pdbsum/5zft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zft ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5zft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zft OCA], [http://pdbe.org/5zft PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zft RCSB], [http://www.ebi.ac.uk/pdbsum/5zft PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zft ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/BLAC_BACLI BLAC_BACLI] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Clostridium licheniforme weigmann 1898]] | + | [[Category: Bacillus licheniformis]] |
| - | [[Category: Beta-lactamase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pan, X]] | + | [[Category: Pan X]] |
| - | [[Category: Zhao, Y]] | + | [[Category: Zhao Y]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Class a beta-lactamase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
BLAC_BACLI
Publication Abstract from PubMed
Serine-based beta-lactamases of Class A, C and D all rely on a key water molecule to hydrolyze and inactivate beta-lactam antibiotics. This process involves two conserved catalytic steps. In the first acylation step, the beta-lactam antibiotic forms an acyl-enzyme intermediate (ES*) with the catalytic serine residue. In the second deacylation step, an activated water molecule serves as nucleophile (WAT_Nu) to attack ES* and release the inactivated beta-lactam. The coordination and activation of WAT_Nu is not fully understood. Using time-resolved x-ray crystallography and QM/MM simulations, we analyzed three intermediate structures of Class A beta-lactamase PenP as it slowly hydrolyzed cephaloridine. WAT_Nu is centrally located in the apo structure but becomes slightly displaced away by ES* in the post-acylation structure. In the deacylation structure, WAT_Nu moves back and is positioned along the Burgi-Dunitz trajectory with favorable energetic profile to attack ES*. Unexpectedly, WAT_Nu is also found to adopt a catalytically incompetent conformation in the deacylation structure forming a hydrogen bond with ES*. Our results reveal that ES* plays a significant role in coordinating and activating WAT_Nu through subtle yet distinct interactions at different stages of the catalytic process. These interactions may serve as potential targets to circumvent beta-lactamase-mediated antibiotic resistance.
The hydrolytic water molecule of Class A beta-lactamase relies on the acyl-enzyme intermediate ES* for proper coordination and catalysis.,He Y, Lei J, Pan X, Huang X, Zhao Y Sci Rep. 2020 Jun 23;10(1):10205. doi: 10.1038/s41598-020-66431-w. PMID:32576842[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ He Y, Lei J, Pan X, Huang X, Zhao Y. The hydrolytic water molecule of Class A beta-lactamase relies on the acyl-enzyme intermediate ES* for proper coordination and catalysis. Sci Rep. 2020 Jun 23;10(1):10205. doi: 10.1038/s41598-020-66431-w. PMID:32576842 doi:http://dx.doi.org/10.1038/s41598-020-66431-w
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