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| | <StructureSection load='6vnu' size='340' side='right'caption='[[6vnu]], [[Resolution|resolution]] 1.47Å' scene=''> | | <StructureSection load='6vnu' size='340' side='right'caption='[[6vnu]], [[Resolution|resolution]] 1.47Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vnu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VNU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VNU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vnu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VNU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VNU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7G4:ruthenocene'>7G4</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TDJ:[(1,2,3,4,5-eta)-1-(4-{[carboxy(4-carboxy-5-methylidene-5,6-dihydro-2H-1,3-thiazin-2-yl)methyl]amino}-4-oxobutanoyl)cyclopentadienyl][(1,2,3,4,5-eta)-cyclopentadienyl]ruthenium'>TDJ</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]] 1.47Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaCTX-M, CTX-M-14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7G4:ruthenocene'>7G4</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TDJ:[(1,2,3,4,5-eta)-1-(4-{[carboxy(4-carboxy-5-methylidene-5,6-dihydro-2H-1,3-thiazin-2-yl)methyl]amino}-4-oxobutanoyl)cyclopentadienyl][(1,2,3,4,5-eta)-cyclopentadienyl]ruthenium'>TDJ</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=6vnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vnu OCA], [https://pdbe.org/6vnu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vnu RCSB], [https://www.ebi.ac.uk/pdbsum/6vnu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vnu 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=6vnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vnu OCA], [http://pdbe.org/6vnu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vnu RCSB], [http://www.ebi.ac.uk/pdbsum/6vnu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vnu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q9L5C7_ECOLX Q9L5C7_ECOLX] |
| | <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: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Beta-lactamase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, Y]] | + | [[Category: Chen Y]] |
| - | [[Category: Jacobs, L M.C]] | + | [[Category: Jacobs LMC]] |
| - | [[Category: Lewandowski, E M]] | + | [[Category: Lewandowski EM]] |
| - | [[Category: Ctx-m-14]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Organometallic]]
| + | |
| Structural highlights
Function
Q9L5C7_ECOLX
Publication Abstract from PubMed
Here, we report the antibacterial properties of two metallocenyl (ferrocenyl and ruthenocenyl) 7-aminocephalosporanic acid (7-ACA) antibiotic bioorganometallic conjugates. Continuing a trend we found in our previous studies, the ruthenocenyl conjugate showed greater antibacterial activity than its ferrocenyl counterpart. Compared with the previously published 7-aminodesacetoxycephalosporanic acid (7-ADCA) conjugates, the 3-acetyloxymethyl group significantly improved the compounds' activity. Furthermore, the Rc-7-ACA compound was more active against clinical S. aureus isolates than the ampicillin reference. Antibacterial activity of the two metallocenyl 7-ACA derivatives was further confirmed by scanning electron microscopy (SEM). Using a CTX-M-14 beta-lactamase competition assay based on nitrocefin hydrolysis, we showed that the Rc-7-ACA bound more favorably to CTX-M-14 than its ferrocenyl counterpart, again confirming the superiority of the ruthenocenyl moiety over the ferrocenyl one in interacting with proteins. We also report a 1.47 A resolution crystal structure of Rc-7-ACA in complex with CTX-M-14 E166A mutant, an enzyme sharing a similar active site configuration with penicillin-binding proteins, the molecular target of beta-lactam antibiotics. These results strengthen the case for the antibacterial utility of the Rc and Fc groups.
Metallocenyl 7-ACA Conjugates: Antibacterial Activity Studies and Atomic-Resolution X-ray Crystal Structure with CTX-M beta-Lactamase.,Lewandowski EM, Szczupak L, Kowalczyk A, Mendoza G, Arruebo M, Jacobs LMC, Staczek P, Chen Y, Kowalski K Chembiochem. 2020 Mar 17. doi: 10.1002/cbic.202000054. PMID:32182393[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lewandowski EM, Szczupak L, Kowalczyk A, Mendoza G, Arruebo M, Jacobs LMC, Staczek P, Chen Y, Kowalski K. Metallocenyl 7-ACA Conjugates: Antibacterial Activity Studies and Atomic-Resolution X-ray Crystal Structure with CTX-M beta-Lactamase. Chembiochem. 2020 Mar 17. doi: 10.1002/cbic.202000054. PMID:32182393 doi:http://dx.doi.org/10.1002/cbic.202000054
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