5fq9: Difference between revisions
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==Crystal structure of the OXA10 with 1C== | |||
<StructureSection load='5fq9' size='340' side='right'caption='[[5fq9]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5fq9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FQ9 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=C6S:(3R)-3-(CYCLOHEXYLCARBONYLAMINO)-2-OXIDANYL-3,4-DIHYDRO-1,2-BENZOXABORININE-8-CARBOXYLIC+ACID'>C6S</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5fq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fq9 OCA], [https://pdbe.org/5fq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fq9 RCSB], [https://www.ebi.ac.uk/pdbsum/5fq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fq9 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BLO10_PSEAI BLO10_PSEAI] Hydrolyzes both carbenicillin and oxacillin. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
beta-Lactamases enable resistance to almost all beta-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as 'transition state analogue' inhibitors of nucleophilic serine enzymes, including serine-beta-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent beta-lactamases by a mechanism involving mimicking of the common tetrahedral intermediate. Cyclic boronates also potently inhibit the non-essential penicillin-binding protein PBP 5 by the same mechanism of action. The results open the way for development of dual action inhibitors effective against both serine- and metallo-beta-lactamases, and which could also have antimicrobial activity through inhibition of PBPs. | |||
Structural basis of metallo-beta-lactamase, serine-beta-lactamase and penicillin-binding protein inhibition by cyclic boronates.,Brem J, Cain R, Cahill S, McDonough MA, Clifton IJ, Jimenez-Castellanos JC, Avison MB, Spencer J, Fishwick CW, Schofield CJ Nat Commun. 2016 Aug 8;7:12406. doi: 10.1038/ncomms12406. PMID:27499424<ref>PMID:27499424</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5fq9" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Cain | ==See Also== | ||
[[Category: | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa]] | |||
[[Category: Brem J]] | |||
[[Category: Cain R]] | |||
[[Category: Clifton I]] | |||
[[Category: Fishwick CWG]] | |||
[[Category: McDonough MA]] | |||
[[Category: Schofield CJ]] | |||
Latest revision as of 16:18, 26 July 2023
Crystal structure of the OXA10 with 1CCrystal structure of the OXA10 with 1C
Structural highlights
FunctionBLO10_PSEAI Hydrolyzes both carbenicillin and oxacillin. Publication Abstract from PubMedbeta-Lactamases enable resistance to almost all beta-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as 'transition state analogue' inhibitors of nucleophilic serine enzymes, including serine-beta-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent beta-lactamases by a mechanism involving mimicking of the common tetrahedral intermediate. Cyclic boronates also potently inhibit the non-essential penicillin-binding protein PBP 5 by the same mechanism of action. The results open the way for development of dual action inhibitors effective against both serine- and metallo-beta-lactamases, and which could also have antimicrobial activity through inhibition of PBPs. Structural basis of metallo-beta-lactamase, serine-beta-lactamase and penicillin-binding protein inhibition by cyclic boronates.,Brem J, Cain R, Cahill S, McDonough MA, Clifton IJ, Jimenez-Castellanos JC, Avison MB, Spencer J, Fishwick CW, Schofield CJ Nat Commun. 2016 Aug 8;7:12406. doi: 10.1038/ncomms12406. PMID:27499424[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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