6i30: Difference between revisions
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==Crystal structure of the AmpC from Pseudomonas aeruginosa with 1C== | |||
<StructureSection load='6i30' size='340' side='right' caption='[[6i30]], [[Resolution|resolution]] 2.21Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6i30]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I30 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I30 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C6S:(3R)-3-(CYCLOHEXYLCARBONYLAMINO)-2-OXIDANYL-3,4-DIHYDRO-1,2-BENZOXABORININE-8-CARBOXYLIC+ACID'>C6S</scene></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=6i30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i30 OCA], [http://pdbe.org/6i30 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i30 RCSB], [http://www.ebi.ac.uk/pdbsum/6i30 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i30 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BACKGROUND: The beta-lactam antibiotics represent the most successful drug class for treatment of bacterial infections. Resistance to them, importantly via production of beta-lactamases, which collectively are able to hydrolyse all classes of beta-lactams, threatens their continued widespread use. Bicyclic boronates show potential as broad spectrum inhibitors of the mechanistically distinct serine- (SBL) and metallo- (MBL) beta-lactamase families. METHODS: Using biophysical methods, including crystallographic analysis, we have investigated the binding mode of bicyclic boronates to clinically important beta-lactamases. Induction experiments and agar-based MIC screening against MDR-Enterobacteriaceae (n=132) were used to evaluate induction properties and the in vitro efficacy of a bicyclic boronate in combination with meropenem. RESULTS: Crystallographic analysis of a bicyclic boronate in complex with AmpC from Pseudomonas aeruginosa reveals it binds to form a tetrahedral boronate species. Microbiological studies on the clinical coverage (in combination with meropenem) and induction of beta-lactamases by bicyclic boronates further support the promise of such compounds as broad spectrum beta-lactamase inhibitors. CONCLUSIONS: Together with reported studies on the structural basis of their inhibition of class A, B and D beta-lactamases, biophysical studies, including crystallographic analysis, support the proposal that bicyclic boronates mimic tetrahedral intermediates common to SBL and MBL catalysis. GENERAL SIGNIFICANCE: Bicyclic boronates are a new generation of broad spectrum inhibitors of both SBLs and MBLs. | |||
Studies on the inhibition of AmpC and other beta-lactamases by cyclic boronates.,Cahill ST, Tyrrell JM, Navratilova IH, Calvopina K, Robinson SW, Lohans CT, McDonough MA, Cain R, Fishwick CWG, Avison MB, Walsh TR, Schofield CJ, Brem J Biochim Biophys Acta Gen Subj. 2019 Apr;1863(4):742-748. doi:, 10.1016/j.bbagen.2019.02.004. Epub 2019 Feb 7. PMID:30738906<ref>PMID:30738906</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6i30" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Brem, J]] | [[Category: Brem, J]] | ||
[[Category: Cahill, S | [[Category: Cahill, S T]] | ||
[[Category: | [[Category: McDonough, M A]] | ||
[[Category: Schofield, C | [[Category: Schofield, C J]] | ||
[[Category: Antibiotic]] | |||
[[Category: Antimicrobial resistance]] | |||
[[Category: Beta-lactamase]] | |||
[[Category: Cyclic boronate]] | |||
[[Category: Hydrolase]] | |||
Revision as of 06:46, 21 February 2019
Crystal structure of the AmpC from Pseudomonas aeruginosa with 1C
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