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| | ==Crystal structure of extended-spectrum beta-lactamase BEL-1 (orthorhombic form)== | | ==Crystal structure of extended-spectrum beta-lactamase BEL-1 (orthorhombic form)== |
| - | <StructureSection load='5eoe' size='340' side='right' caption='[[5eoe]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='5eoe' size='340' side='right'caption='[[5eoe]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5eoe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4mx4 4mx4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EOE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EOE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5eoe]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4mx4 4mx4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EOE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EOE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla(BEL1), blaBEL-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=5eoe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eoe OCA], [https://pdbe.org/5eoe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eoe RCSB], [https://www.ebi.ac.uk/pdbsum/5eoe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eoe ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5eoe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eoe OCA], [http://pdbe.org/5eoe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5eoe RCSB], [http://www.ebi.ac.uk/pdbsum/5eoe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5eoe ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q3SAW3_PSEAI Q3SAW3_PSEAI] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5eoe" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5eoe" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Large Structures]] |
| - | [[Category: Benvenuti, M]]
| + | |
| - | [[Category: Docquier, J D]]
| + | |
| - | [[Category: Luca, F De]]
| + | |
| - | [[Category: Mangani, S]]
| + | |
| - | [[Category: Pozzi, C]]
| + | |
| - | [[Category: Citrate]]
| + | |
| - | [[Category: Extended-spectrum beta-lactamase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Native]]
| + | |
| | [[Category: Pseudomonas aeruginosa]] | | [[Category: Pseudomonas aeruginosa]] |
| | + | [[Category: Benvenuti M]] |
| | + | [[Category: De Luca F]] |
| | + | [[Category: Docquier JD]] |
| | + | [[Category: Mangani S]] |
| | + | [[Category: Pozzi C]] |
| Structural highlights
5eoe is a 2 chain structure with sequence from Pseudomonas aeruginosa. This structure supersedes the now removed PDB entry 4mx4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.6Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q3SAW3_PSEAI
Publication Abstract from PubMed
BEL-1 is an acquired class A ESBL found in P. aeruginosa clinical isolates from Belgium, which is divergent from other ESBLs (max. identity, 54% with GES-type enzymes). This enzyme is efficiently inhibited by clavulanate, imipenem and moxalactam. Crystals of BEL-1 were obtained at pH 5.6 and the structure of native BEL-1 was determined from orthorhombic and monoclinic crystal forms, at 1.60-A and 1.48 A resolution, respectively. By soaking native BEL-1 crystals, complexes with imipenem (monoclinic form, 1.79 A res.) and moxalactam (orthorhombic form, 1.85 A res.) were also obtained. In the acyl-enzyme complexes, imipenem and moxalactam differ by the position of the alpha-substituent and of the carbonyl oxygen (in or out the oxyanion hole). More surprisingly, the Omega-loop, which includes the catalytically-relevant residue Glu166, was found in different conformations in the various subunits, resulting in the Glu166 side chain to be rotated outwards the active site or even in displacements of its Calpha atom up to approx. 10 A. A BEL-1 variant showing the single Leu162Phe substitution (BEL-2) confers a higher level of resistance to CAZ, CTX and FEP and shows significantly lower KM values as compared to those of BEL-1, especially with oxyiminocephalosporins. BEL-1 Leu162 is located at the beginning of the Omega-loop, and surrounded by Phe72, Leu139, Leu148 and Leu169 (contact distances, 3.8-4.0 A). This small hydrophobic cavity could not reasonably accommodate the bulkier Phe162 found in BEL-2 without altering neighboring residues or the Omega-loop itself, thus likely causing an important alteration of the enzyme kinetic properties.
Crystal Structure of the Pseudomonas aeruginosa BEL-1 Extended-Spectrum beta-Lactamase and its Complex with Moxalactam and Imipenem.,Pozzi C, De Luca F, Benvenuti M, Poirel L, Nordmann P, Rossolini GM, Mangani S, Docquier JD Antimicrob Agents Chemother. 2016 Sep 26. pii: AAC.00936-16. PMID:27671060[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pozzi C, De Luca F, Benvenuti M, Poirel L, Nordmann P, Rossolini GM, Mangani S, Docquier JD. Crystal Structure of the Pseudomonas aeruginosa BEL-1 Extended-Spectrum beta-Lactamase and its Complex with Moxalactam and Imipenem. Antimicrob Agents Chemother. 2016 Sep 26. pii: AAC.00936-16. PMID:27671060 doi:http://dx.doi.org/10.1128/AAC.00936-16
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