9BIS

Cryo-EM structure of the mammalian peptide transporter PepT2 bound to amoxicillin

9BIS の概要

• エントリーDOI: 10.2210/pdb9bis/pdb
• EMDBエントリー: 44600
• 分子名称: Solute carrier family 15 member 2, nanobody, 2-{1-[2-AMINO-2-(4-HYDROXY-PHENYL)-ACETYLAMINO]-2-OXO-ETHYL}-5,5-DIMETHYL-THIAZOLIDINE-4-CARBOXYLIC ACID (3 entities in total)
• 機能のキーワード: protein-coupled peptide transporter, peptide transport, antibiotics, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97339.37

構造登録者

Parker, J.L.,Deme, J.C.,Lea, S.M.,Newstead, S. (登録日: 2024-04-24, 公開日: 2024-07-24, 最終更新日: 2024-11-13)

主引用文献

Parker, J.L.,Deme, J.C.,Lichtinger, S.M.,Kuteyi, G.,Biggin, P.C.,Lea, S.M.,Newstead, S.
Structural basis for antibiotic transport and inhibition in PepT2.
Nat Commun, 15:8755-8755, 2024

PubMed Abstract: The uptake and elimination of beta-lactam antibiotics in the human body are facilitated by the proton-coupled peptide transporters PepT1 (SLC15A1) and PepT2 (SLC15A2). The mechanism by which SLC15 family transporters recognize and discriminate between different drug classes and dietary peptides remains unclear, hampering efforts to improve antibiotic pharmacokinetics through targeted drug design and delivery. Here, we present cryo-EM structures of the proton-coupled peptide transporter, PepT2 from Rattus norvegicus, in complex with the widely used beta-lactam antibiotics cefadroxil, amoxicillin and cloxacillin. Our structures, combined with pharmacophore mapping, molecular dynamics simulations and biochemical assays, establish the mechanism of beta-lactam antibiotic recognition and the important role of protonation in drug binding and transport.

PubMed: 39384780
DOI: 10.1038/s41467-024-53096-6

実験手法

ELECTRON MICROSCOPY (3.2 Å)