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-Structure paper
| タイトル | Structural and functional insights of AmpG in muropeptide transport and multiple β-lactam antibiotics resistance. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 5744, Year 2025 |
| 掲載日 | 2025年7月1日 |
著者 | Nienping Chang / Hoyoung Kim / Uijin Kim / Yongju Cho / Youngki Yoo / Hyunsook Lee / Ji Won Kim / Min Sung Kim / Jaeho Lee / Young-Lag Cho / Kitae Kim / Dongeun Yong / Hyun-Soo Cho / ![]() |
| PubMed 要旨 | 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. ...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. |
リンク | Nat Commun / PubMed:40593790 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.97 - 3.88 Å |
| 構造データ | EMDB-39900, PDB-8zbb: EMDB-60093, PDB-8zgz: EMDB-60190, PDB-8zke: EMDB-61285, PDB-9j9z: |
| 化合物 | ![]() ChemComp-2YP: |
| 由来 |
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キーワード | PEPTIDE BINDING PROTEIN / transporter / ampg / cryo-em / permease / TRANSPORT PROTEIN / antibiotic resistance / membrane transporter / MEMBRANE PROTEIN / MFS / Anhydromuropeptide permease |
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yokenella regensburgei (バクテリア)
homo sapiens (ヒト)
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