7a1e: Difference between revisions
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New page: '''Unreleased structure''' The entry 7a1e is ON HOLD Authors: Description: Category: Unreleased Structures |
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==LppS with covalent adduct derived from 1c== | |||
<StructureSection load='7a1e' size='340' side='right'caption='[[7a1e]], [[Resolution|resolution]] 1.77Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A1E 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]] 1.77Å</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=SDQ:phenylmethanethiol'>SDQ</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=7a1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a1e OCA], [https://pdbe.org/7a1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a1e RCSB], [https://www.ebi.ac.uk/pdbsum/7a1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a1e ProSAT]</span></td></tr> | |||
</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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7a1e" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Schnell R]] | |||
[[Category: Steiner EM]] | |||
