7QS6

Solution structure of thanatin-like derivative 7 in complex with E.coli LptA

7QS6 の概要

• エントリーDOI: 10.2210/pdb7qs6/pdb
• NMR情報: BMRB: 34699
• 分子名称: Lipopolysaccharide export system protein LptA, Thanatin-like derivative (2 entities in total)
• 機能のキーワード: structure from cyana 3.98.11, antibiotic
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 14875.69

構造登録者

Moehle, K.,Zerbe, O. (登録日: 2022-01-12, 公開日: 2023-05-10, 最終更新日: 2023-11-15)

主引用文献

Schuster, M.,Brabet, E.,Oi, K.K.,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.
Peptidomimetic antibiotics disrupt the lipopolysaccharide transport bridge of drug-resistant Enterobacteriaceae.
Sci Adv, 9:eadg3683-eadg3683, 2023

PubMed Abstract: 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 and strains with low-nanomolar affinities. Mode of action studies revealed that the antimicrobial activity involves the specific disruption of the Lpt periplasmic protein bridge.

PubMed: 37224246
DOI: 10.1126/sciadv.adg3683

実験手法

SOLUTION NMR