8ADI

Cryo-EM structure of Darobactin 9 bound BAM complex

8ADI の概要

• エントリーDOI: 10.2210/pdb8adi/pdb
• EMDBエントリー: 15363
• 関連するBIRD辞書のPRD_ID: PRD_002430
• 分子名称: Outer membrane protein assembly factor BamA, Outer membrane protein assembly factor BamB, Outer membrane protein assembly factor BamC, ... (6 entities in total)
• 機能のキーワード: bam complex; darobactin 9, structural protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 214349.35

構造登録者

Yuan, B.,Marlovits, T.C. (登録日: 2022-07-08, 公開日: 2023-01-11, 最終更新日: 2024-11-20)

主引用文献

Seyfert, C.E.,Porten, C.,Yuan, B.,Deckarm, S.,Panter, F.,Bader, C.D.,Coetzee, J.,Deschner, F.,Tehrani, K.H.M.E.,Higgins, P.G.,Seifert, H.,Marlovits, T.C.,Herrmann, J.,Muller, R.
Darobactins Exhibiting Superior Antibiotic Activity by Cryo-EM Structure Guided Biosynthetic Engineering.
Angew.Chem.Int.Ed.Engl., 62:e202214094-e202214094, 2023

PubMed Abstract: Over recent decades, the pipeline of antibiotics acting against Gram-negative bacteria is running dry, as most discovered candidate antibiotics suffer from insufficient potency, pharmacokinetic properties, or toxicity. The darobactins, a promising new small peptide class of drug candidates, bind to novel antibiotic target BamA, an outer membrane protein. Previously, we reported that biosynthetic engineering in a heterologous host generated novel darobactins with enhanced antibacterial activity. Here we utilize an optimized purification method and present cryo-EM structures of the Bam complex with darobactin 9 (D9), which served as a blueprint for the biotechnological generation of twenty new darobactins including halogenated analogs. The newly engineered darobactin 22 binds more tightly to BamA and outperforms the favorable activity profile of D9 against clinically relevant pathogens such as carbapenem-resistant Acinetobacter baumannii up to 32-fold, without observing toxic effects.

PubMed: 36308277
DOI: 10.1002/anie.202214094

実験手法

ELECTRON MICROSCOPY (3.4 Å)