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| | <StructureSection load='5dtk' size='340' side='right'caption='[[5dtk]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='5dtk' size='340' side='right'caption='[[5dtk]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dtk]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DTK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DTK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dtk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DTK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DTK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5F3:3,5-DI(PYRIDIN-4-YL)BENZOIC+ACID'>5F3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.6000024Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5F3:3,5-DI(PYRIDIN-4-YL)BENZOIC+ACID'>5F3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dva|5dva]]</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=5dtk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dtk OCA], [https://pdbe.org/5dtk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dtk RCSB], [https://www.ebi.ac.uk/pdbsum/5dtk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dtk ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla OXA-48, blaOXA-48, KPE71T_00045 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</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://proteopedia.org/fgij/fg.htm?mol=5dtk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dtk OCA], [http://pdbe.org/5dtk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dtk RCSB], [http://www.ebi.ac.uk/pdbsum/5dtk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dtk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN] |
| | <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: Klebsiella pneumoniae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Christopeit, T]] | + | [[Category: Christopeit T]] |
| - | [[Category: Leiros, H K.S]] | + | [[Category: Leiros H-KS]] |
| - | [[Category: Lund, B A]] | + | [[Category: Lund BA]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Fragment]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Lactamase]]
| + | |
| Structural highlights
Function
Q6XEC0_KLEPN
Publication Abstract from PubMed
The spread of antibiotic resistant bacteria is a global threat that shakes the foundations of modern healthcare. beta-Lactamases are enzymes that confer resistance to beta-lactam antibiotics in bacteria, and there is a critical need for new inhibitors of these enzymes for combination therapy together with an antibiotic. With this in mind, we have screened a library of 490 fragments to identify starting points for the development of new inhibitors of the class D beta-lactamase oxacillinase-48 (OXA-48) through surface plasmon resonance (SPR), dose-rate inhibition assays, and X-ray crystallography. Furthermore, we have uncovered structure-activity relationships and used alternate conformations from a crystallographic structure to grow a fragment into a more potent compound with a KD of 50 muM and an IC50 of 18 muM.
Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening.,Lund BA, Christopeit T, Guttormsen Y, Bayer A, Leiros HS J Med Chem. 2016 May 20. PMID:27165692[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lund BA, Christopeit T, Guttormsen Y, Bayer A, Leiros HS. Screening and Design of Inhibitor Scaffolds for the Antibiotic Resistance Oxacillinase-48 (OXA-48) through Surface Plasmon Resonance Screening. J Med Chem. 2016 May 20. PMID:27165692 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00660
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