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| | <StructureSection load='3m2k' size='340' side='right'caption='[[3m2k]], [[Resolution|resolution]] 3.50Å' scene=''> | | <StructureSection load='3m2k' size='340' side='right'caption='[[3m2k]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3m2k]] is a 2 chain structure with sequence from [https://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=3M2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M2K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3m2k]] 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=3M2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M2K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CEF:CEFOTAXIME,+C3+CLEAVED,+OPEN,+BOUND+FORM'>CEF</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]] 3.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ly3|3ly3]], [[3ly4|3ly4]], [[3m2j|3m2j]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CEF:CEFOTAXIME,+C3+CLEAVED,+OPEN,+BOUND+FORM'>CEF</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">penP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1402 "Clostridium licheniforme" Weigmann 1898])</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=3m2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m2k OCA], [https://pdbe.org/3m2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m2k RCSB], [https://www.ebi.ac.uk/pdbsum/3m2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m2k 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=3m2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m2k OCA], [https://pdbe.org/3m2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m2k RCSB], [https://www.ebi.ac.uk/pdbsum/3m2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m2k 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: Leung, Y C]] | + | [[Category: Leung YC]] |
| - | [[Category: Wong, W T]] | + | [[Category: Wong WT]] |
| - | [[Category: Zhao, Y X]] | + | [[Category: Zhao YX]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Biosensor]]
| + | |
| - | [[Category: Cefotaxime]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Fluorophore]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Palmitate]]
| + | |
| Structural highlights
Function
BLAC_BACLI
Publication Abstract from PubMed
BACKGROUND: beta-lactamase conjugated with environment-sensitive fluorescein molecule to residue 166 on the Omega-loop near its catalytic site is a highly effective biosensor for beta-lactam antibiotics. Yet the molecular mechanism of such fluorescence-based biosensing is not well understood. RESULTS: Here we report the crystal structure of a Class A beta-lactamase PenP from Bacillus licheniformis 749/C with fluorescein conjugated at residue 166 after E166C mutation, both in apo form (PenP-E166Cf) and in covalent complex form with cefotaxime (PenP-E166Cf-cefotaxime), to illustrate its biosensing mechanism. In the apo structure the fluorescein molecule partially occupies the antibiotic binding site and is highly dynamic. In the PenP-E166Cf-cefatoxime complex structure the binding and subsequent acylation of cefotaxime to PenP displaces fluorescein from its original location to avoid steric clash. Such displacement causes the well-folded Omega-loop to become fully flexible and the conjugated fluorescein molecule to relocate to a more solvent exposed environment, hence enhancing its fluorescence emission. Furthermore, the fully flexible Omega-loop enables the narrow-spectrum PenP enzyme to bind cefotaxime in a mode that resembles the extended-spectrum beta-lactamase. CONCLUSIONS: Our structural studies indicate the biosensing mechanism of a fluorescein-labelled beta-lactamase. Such findings confirm our previous proposal based on molecular modelling and provide useful information for the rational design of beta-lactamase-based biosensor to detect the wide spectrum of beta-lactam antibiotics. The observation of increased Omega-loop flexibility upon conjugation of fluorophore may have the potential to serve as a screening tool for novel beta-lactamase inhibitors that target the Omega-loop and not the active site.
Structural studies of the mechanism for biosensing antibiotics in a fluorescein-labeled beta-lactamase.,Wong WT, Au HW, Yap HK, Leung YC, Wong KY, Zhao Y BMC Struct Biol. 2011 Mar 28;11:15. doi: 10.1186/1472-6807-11-15. PMID:21443768[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wong WT, Au HW, Yap HK, Leung YC, Wong KY, Zhao Y. Structural studies of the mechanism for biosensing antibiotics in a fluorescein-labeled beta-lactamase. BMC Struct Biol. 2011 Mar 28;11:15. doi: 10.1186/1472-6807-11-15. PMID:21443768 doi:http://dx.doi.org/10.1186/1472-6807-11-15
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