4jxw
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4jxw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JXW FirstGlance]. <br> | <table><tr><td colspan='2'>[[4jxw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JXW FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1MW:3-{[3-(4-CARBOXYPHENYL)PROPYL]SULFAMOYL}THIOPHENE-2-CARBOXYLIC+ACID'>1MW</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1MW:3-{[3-(4-CARBOXYPHENYL)PROPYL]SULFAMOYL}THIOPHENE-2-CARBOXYLIC+ACID'>1MW</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4jxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jxw OCA], [https://pdbe.org/4jxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jxw RCSB], [https://www.ebi.ac.uk/pdbsum/4jxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jxw ProSAT]</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=4jxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jxw OCA], [https://pdbe.org/4jxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jxw RCSB], [https://www.ebi.ac.uk/pdbsum/4jxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jxw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. | [https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | beta-Lactams are the most widely prescribed class of antibiotics, yet their efficacy is threatened by expression of beta-lactamase enzymes, which hydrolyze the defining lactam ring of these antibiotics. To overcome resistance due to beta-lactamases, inhibitors that do not resemble beta-lactams are needed. A novel, non-beta-lactam inhibitor for the class C beta-lactamase AmpC (3-[(4-chloroanilino)sulfonyl]thiophene-2-carboxylic acid; Ki 26muM) was previously identified. Based on this lead, a series of compounds with the potential to interact with residues at the edge of the active site were synthesized and tested for inhibition of AmpC. The length of the carbon chain spacer was extended by 1, 2, 3, and 4 carbons between the integral thiophene ring and the benzene ring (compounds 4, 5, 6, and 7). Compounds 4 and 6 showed minimal improvement over the lead compound (Ki 18 and 19muM, respectively), and compound 5 inhibited to the same extent as the lead. The X-ray crystal structures of AmpC in complexes with compounds 4, 5, and 6 were determined. The complexes provide insight into the structural reasons for the observed inhibition, and inform future optimization efforts in this series. | ||
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| - | Structure-based efforts to optimize a non-beta-lactam inhibitor of AmpC beta-lactamase.,Hendershot JM, Mishra UJ, Smart RP, Schroeder W, Powers RA Bioorg Med Chem. 2014 Jul 1;22(13):3351-9. doi: 10.1016/j.bmc.2014.04.051. Epub, 2014 May 5. PMID:24835785<ref>PMID:24835785</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4jxw" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a non-covalent inhibitor 3-{[3-(4-CARBOXYPHENYL)PROPYL]SULFAMOYL}THIOPHENE-2-CARBOXYLIC ACID (compound 6)
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