4jxv
From Proteopedia
(Difference between revisions)
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<StructureSection load='4jxv' size='340' side='right' caption='[[4jxv]], [[Resolution|resolution]] 1.76Å' scene=''> | <StructureSection load='4jxv' size='340' side='right' caption='[[4jxv]], [[Resolution|resolution]] 1.76Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4jxv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JXV OCA]. <br> | + | <table><tr><td colspan='2'>[[4jxv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JXV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JXV FirstGlance]. <br> |
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1MU:3-{[2-(4-CARBOXYPHENYL)ETHYL]SULFAMOYL}THIOPHENE-2-CARBOXYLIC+ACID'>1MU</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br> | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1MU:3-{[2-(4-CARBOXYPHENYL)ETHYL]SULFAMOYL}THIOPHENE-2-CARBOXYLIC+ACID'>1MU</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jxs|4jxs]], [[1l2s|1l2s]], [[1xgi|1xgi]], [[1xgj|1xgj]], [[4jxw|4jxw]]</td></tr> | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jxs|4jxs]], [[1l2s|1l2s]], [[1xgi|1xgi]], [[1xgj|1xgj]], [[4jxw|4jxw]]</td></tr> | ||
| - | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/ | + | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ampC, ampA, b4150, JW4111 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> |
| + | <tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jxv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jxv RCSB], [http://www.ebi.ac.uk/pdbsum/4jxv PDBsum]</span></td></tr> | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jxv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jxv RCSB], [http://www.ebi.ac.uk/pdbsum/4jxv PDBsum]</span></td></tr> | ||
<table> | <table> | ||
| + | <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. | ||
| + | |||
| + | 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> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
| + | [[Category: Ecoli]] | ||
[[Category: Hendershot, J M.]] | [[Category: Hendershot, J M.]] | ||
[[Category: Powers, R A.]] | [[Category: Powers, R A.]] | ||
Revision as of 06:09, 2 July 2014
X-ray crystal structure of AmpC beta-lactamase from E. coli in complex with a non-covalent inhibitor 3-{[2-(4-CARBOXYPHENYL)ETHYL]SULFAMOYL}THIOPHENE-2-CARBOXYLIC ACID (compound 5)
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