7zax | pdb_00007zax

Solution structure of thanatin-like derivative 7 in complex with K. pneumoniae LptA

spinqualitylabelsall models 7zax Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7zax is a 2 chain structure with sequence from Klebsiella pneumoniae and Podisus maculiventris. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 4FO, DAB, EU0, HYP, LE1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A6TEL9_KLEP7 Involved in the assembly of lipopolysaccharide (LPS). Required for the translocation of LPS from the inner membrane to the outer membrane. May form a bridge between the inner membrane and the outer membrane, via interactions with LptC and LptD, thereby facilitating LPS transfer across the periplasm.[HAMAP-Rule:MF_01914] Publication Abstract from PubMed The rise of antimicrobial resistance poses a substantial threat to our health system, and, hence, development of drugs against novel targets is urgently needed. The natural peptide thanatin kills Gram-negative bacteria by targeting proteins of the lipopolysaccharide transport (Lpt) machinery. Using the thanatin scaffold together with phenotypic medicinal chemistry, structural data, and a target-focused approach, we developed antimicrobial peptides with drug-like properties. They exhibit potent activity against Enterobacteriaceae both in vitro and in vivo while eliciting low frequencies of resistance. We show that the peptides bind LptA of both wild-type and thanatin-resistant Escherichia coli and Klebsiella pneumoniae strains with low-nanomolar affinities. Mode of action studies revealed that the antimicrobial activity involves the specific disruption of the Lpt periplasmic protein bridge. Peptidomimetic antibiotics disrupt the lipopolysaccharide transport bridge of drug-resistant Enterobacteriaceae.,Schuster M, Brabet E, Oi KK, Desjonqueres N, Moehle K, Le Poupon K, Hell S, Gable S, Rithie V, Dillinger S, Zbinden P, Luther A, Li C, Stiegeler S, D'Arco C, Locher H, Remus T, DiMaio S, Motta P, Wach A, Jung F, Upert G, Obrecht D, Benghezal M, Zerbe O Sci Adv. 2023 May 24;9(21):eadg3683. doi: 10.1126/sciadv.adg3683. Epub 2023 May , 24. PMID:37224246 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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