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''' | ==VIM-2-OX, Discovery of novel inhibitor scaffolds against the metallo- beta-lactamase VIM-2 by SPR based fragment screening== | ||
<StructureSection load='5acv' size='340' side='right' caption='[[5acv]], [[Resolution|resolution]] 1.96Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5acv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ACV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ACV 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=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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5acu|5acu]], [[5acw|5acw]], [[5acx|5acx]]</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=5acv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5acv OCA], [http://pdbe.org/5acv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5acv RCSB], [http://www.ebi.ac.uk/pdbsum/5acv PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:26477515</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5acv" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
[[Category: Carlsen, T | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Beta-lactamase]] | |||
[[Category: Carlsen, T J.O]] | |||
[[Category: Christopeit, T]] | [[Category: Christopeit, T]] | ||
[[Category: Helland, R]] | [[Category: Helland, R]] | ||
[[Category: Leiros, H K.S]] | |||
[[Category: Hydrolase]] | |||