7a10
From Proteopedia
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==LppS with covalent adduct derived from 1g== | ==LppS with covalent adduct derived from 1g== | ||
| - | <StructureSection load='7a10' size='340' side='right'caption='[[7a10]]' scene=''> | + | <StructureSection load='7a10' size='340' side='right'caption='[[7a10]], [[Resolution|resolution]] 1.85Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A10 FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A10 FirstGlance]. <br> | ||
| - | </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=7a10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a10 OCA], [https://pdbe.org/7a10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a10 RCSB], [https://www.ebi.ac.uk/pdbsum/7a10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a10 ProSAT]</span></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]] 1.85Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QU5:4-methoxycyclohexa-2,5-diene-1-thione'>QU5</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=7a10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a10 OCA], [https://pdbe.org/7a10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a10 RCSB], [https://www.ebi.ac.uk/pdbsum/7a10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a10 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Effective treatment of tuberculosis is frequently hindered by the emerging antimicrobial resistance of Mycobacterium tuberculosis. The present study evaluates monocyclic beta-lactam compounds targeting the mycobacterial cell wall remodeling. Novel N-thio-beta-lactams were designed, synthesized, and characterized on the L,D-transpeptidase-2, a validated target in M. tuberculosis. The candidates were evaluated in biochemical assays identifying five compounds presenting target-specific kinetic constants equal or superior to meropenem, a carbapenem currently considered for tuberculosis therapy. Mass spectrometry in line with the crystal structures of five target-ligand complexes revealed that the N-thio-beta-lactams act via an unconventional mode of adduct formation, transferring the thio-residues from the lactam ring to the active-site cysteine of LdtMt2. The resulting stable adducts lead to a long-term inactivation of the target protein. Finally, the candidates were evaluated in vitro against a drug-susceptible and multidrug-resistant clinical isolates of M. tuberculosis, confirming the antimycobacterial effect of these novel compounds. | ||
| + | |||
| + | N-Thio-beta-lactams targeting L,D-transpeptidase-2, with activity against drug-resistant strains of Mycobacterium tuberculosis.,Martelli G, Pessatti TB, Steiner EM, Cirillo M, Caso C, Bisognin F, Landreh M, Monte PD, Giacomini D, Schnell R Cell Chem Biol. 2021 Mar 30. pii: S2451-9456(21)00147-1. doi:, 10.1016/j.chembiol.2021.03.008. PMID:33826941<ref>PMID:33826941</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7a10" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
LppS with covalent adduct derived from 1g
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