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| | <StructureSection load='5acx' size='340' side='right'caption='[[5acx]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='5acx' size='340' side='right'caption='[[5acx]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5acx]] 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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ACX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ACX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5acx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ACX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ACX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</scene>, <scene name='pdbligand=WL3:2-(4-FLUOROPHENYL)CARBONYLBENZOIC+ACID'>WL3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</scene>, <scene name='pdbligand=WL3:2-(4-FLUOROPHENYL)CARBONYLBENZOIC+ACID'>WL3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></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=5acx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5acx OCA], [https://pdbe.org/5acx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5acx RCSB], [https://www.ebi.ac.uk/pdbsum/5acx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5acx ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5acu|5acu]], [[5acv|5acv]], [[5acw|5acw]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5acx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5acx OCA], [http://pdbe.org/5acx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5acx RCSB], [http://www.ebi.ac.uk/pdbsum/5acx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5acx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI] |
| | <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: Beta-lactamase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Carlsen, T J.O]] | + | [[Category: Pseudomonas aeruginosa]] |
| - | [[Category: Christopeit, T]] | + | [[Category: Carlsen TJO]] |
| - | [[Category: Helland, R]] | + | [[Category: Christopeit T]] |
| - | [[Category: Leiros, H K.S]] | + | [[Category: Helland R]] |
| - | [[Category: Hydrolase]] | + | [[Category: Leiros HKS]] |
| Structural highlights
Function
Q9K2N0_PSEAI
Publication Abstract from PubMed
Metallo-beta-lactamase (MBL) inhibitors can restore the function of carbapenem antibiotics and therefore help to treat infections of antibiotic resistant bacteria. In this study, we report novel fragments inhibiting the clinically relevant MBL Verona integron-encoded metallo-beta-lactamase (VIM-2). The fragments were identified from a library of 490 fragments using an orthogonal screening approach based on a surface plasmon resonance (SPR) based assay combined with an enzyme inhibition assay. The identified fragments showed IC50 values between 14 and 1500 muM and ligand efficiencies (LE) between 0.48 and 0.23 kcal/mol per heavy atom. For two of the identified fragments, crystal structures in complex with VIM-2 were obtained. The identified fragments represent novel inhibitor scaffolds and are good starting points for the design of potent MBL inhibitors. Furthermore, the established SPR based assay and the screening approach can be adapted to other MBLs and in this way improve the drug discovery process for this important class of drug targets.
Discovery of Novel Inhibitor Scaffolds against the Metallo-beta-lactamase VIM-2 by Surface Plasmon Resonance (SPR) Based Fragment Screening.,Christopeit T, Carlsen TJ, Helland R, Leiros HK J Med Chem. 2015 Nov 12;58(21):8671-82. doi: 10.1021/acs.jmedchem.5b01289. Epub, 2015 Oct 27. PMID:26477515[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Christopeit T, Carlsen TJ, Helland R, Leiros HK. Discovery of Novel Inhibitor Scaffolds against the Metallo-beta-lactamase VIM-2 by Surface Plasmon Resonance (SPR) Based Fragment Screening. J Med Chem. 2015 Nov 12;58(21):8671-82. doi: 10.1021/acs.jmedchem.5b01289. Epub, 2015 Oct 27. PMID:26477515 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01289
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