8ZKE

Cryo-EM structure of inward-facing Anhydromuropeptide permease (AmpG) in complex with GlcNAc-1,6-anhMurNAc

Summary for 8ZKE

• Entry DOI: 10.2210/pdb8zke/pdb
• EMDB information: 60190
• Descriptor: Muropeptide transporter, (2R)-2-[[(1R,2S,3R,4R,5R)-4-acetamido-2-[(2S,3R,4R,5S,6R)-3-acetamido-6-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-2-yl]oxy-6,8-dioxabicyclo[3.2.1]octan-3-yl]oxy]propanoic acid (2 entities in total)
• Functional Keywords: ampg, mfs, anhydromuropeptide permease, membrane protein
• Biological source: Yokenella regensburgei
• Total number of polymer chains: 1
• Total formula weight: 54547.53

Authors

Chang, N.,Kim, U.,Yoo, Y.,Kim, H.,Cho, H. (deposition date: 2024-05-16, release date: 2025-05-21, 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 (3.72 Å)