8ZBB

Cryo-EM structure of outward state Anhydromuropeptide permease (AmpG) G50W/L269W

Summary for 8ZBB

• Entry DOI: 10.2210/pdb8zbb/pdb
• EMDB information: 39900
• Descriptor: Muropeptide transporter,Soluble cytochrome b562, anti-BRIL Fab Heavy chain, anti-BRIL Fab Nanobody, ... (4 entities in total)
• Functional Keywords: transporter, ampg, cryo-em, permease, peptide binding protein
• Biological source: Yokenella regensburgei; More
• Total number of polymer chains: 4
• Total formula weight: 124044.78

Authors

Yoo, Y.,Chang, N.,Kim, U.,Kim, H.,Cho, H. (deposition date: 2024-04-26, release date: 2025-04-30, Last modification date: 2025-07-16)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.11 Å)