View source for 6fj1


==Structure of the Ldtfm-avibactam carbamoyl enzyme==
<StructureSection load='6fj1' size='340' side='right'caption='[[6fj1]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fj1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecium Enterococcus faecium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FJ1 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]] 2.69&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene>, <scene name='pdbligand=P3G:3,6,9,12,15-PENTAOXAHEPTADECANE'>P3G</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=6fj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fj1 OCA], [https://pdbe.org/6fj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fj1 RCSB], [https://www.ebi.ac.uk/pdbsum/6fj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fj1 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
There is a renewed interest for beta-lactams for treating infections due to Mycobacterium tuberculosis and M. abscessus because their beta-lactamases are inhibited by classical (clavulanate) or new generation (avibactam) inhibitors, respectively. Here, access to an azido derivative of the diazabicyclooctane (DBO) scaffold of avibactam for functionalization by the Huisgen-Sharpless cycloaddition reaction is reported. The amoxicillin-DBO combinations were active, indicating that the triazole ring is compatible with drug penetration (minimal inhibitory concentration of 16 mug mL(-1) for both species). Mechanistically, beta-lactamase inhibition was not sufficient to account for the potentiation of amoxicillin by DBOs. Thus, the latter compounds were investigated as inhibitors of l,d-transpeptidases (Ldts), which are the main peptidoglycan polymerases in mycobacteria. The DBOs acted as slow-binding inhibitors of Ldts by S-carbamoylation indicating that optimization of DBOs for Ldt inhibition is an attractive strategy to obtain drugs selectively active on mycobacteria.

Synthesis of Avibactam Derivatives and Activity on beta-Lactamases and Peptidoglycan Biosynthesis Enzymes of Mycobacteria.,Edoo Z, Iannazzo L, Compain F, Li de la Sierra Gallay I, van Tilbeurgh H, Fonvielle M, Bouchet F, Le Run E, Mainardi JL, Arthur M, Etheve-Quelquejeu M, Hugonnet JE Chemistry. 2018 Jun 7;24(32):8081-8086. doi: 10.1002/chem.201800923. Epub 2018 , May 14. PMID:29601108<ref>PMID:29601108</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fj1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Enterococcus faecium]]
[[Category: Large Structures]]
[[Category: Arthur M]]
[[Category: Compain F]]
[[Category: Edoo Z]]
[[Category: Etheve-Quelquejeu M]]
[[Category: Fonvielle M]]
[[Category: Hugonnet J]]
[[Category: Iannazzo L]]
[[Category: Li de la Sierra Gallay I]]
[[Category: Van Tilbeurgh H]]