9J9Z

Cryo-EM structure of Outward state Anhydromuropeptide permease (AmpG) complex with GlcNAc-1,6-anhMurNAc

9J9Z の概要

• エントリーDOI: 10.2210/pdb9j9z/pdb
• EMDBエントリー: 61285
• 分子名称: anti-BRIL Fab Heavy chain, anti-BRIL Fab Nanobody, anti-BRIL Fab Light chain, ... (5 entities in total)
• 機能のキーワード: ampg, mfs, anhydromuropeptide permease, membrane protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 125473.34

構造登録者

Chang, N.,Kim, U.,Cho, H. (登録日: 2024-08-23, 公開日: 2025-07-16)

主引用文献

Chang, N.,Kim, H.,Kim, U.,Cho, Y.,Yoo, Y.,Lee, H.,Kim, J.W.,Kim, M.S.,Lee, J.,Cho, Y.L.,Kim, K.,Yong, D.,Cho, H.S.
Structural and functional insights of AmpG in muropeptide transport and multiple beta-lactam antibiotics resistance.
Nat Commun, 16:5744-5744, 2025

PubMed Abstract: Anhydromuropeptide permease (AmpG) is a transporter protein located in the inner membrane of certain gram -negative bacteria, involved in peptidoglycan (PG) recycling and β-lactamase induction. Decreased AmpG function reduces resistance of antibiotic-resistant bacteria to β-lactam antibiotics. Therefore, AmpG-targeting inhibitors are promising 'antibiotic adjuvants'. However, as the tertiary structure of AmpG has not yet been identified, the development of targeted inhibitors remains challenging. We present four cryo-electron microscopy (cryo-EM) structures: the apo-inward and apo-outward state structures and the inward-occluded and outward states complexed with the substrate GlcNAc-1,6-anhMurNAc. Through functional analysis and molecular dynamics (MD) simulations, we identified motif A, which stabilizes the outward state, substrate-binding pocket, and protonation-related residues. Based on the structure of AmpG and our experimental results, we propose a muropeptide transport mechanism for AmpG. A deeper understanding of its structure and transport mechanism provides a foundation for the development of antibiotic adjuvants.

PubMed: 40593790
DOI: 10.1038/s41467-025-61169-3

実験手法

ELECTRON MICROSCOPY (2.97 Å)