7Q0M

Crystal structure of the peptide transporter YePEPT-K314A in complex with LZNV at 2.66 A

7Q0M の概要

• エントリーDOI: 10.2210/pdb7q0m/pdb
• 関連するPDBエントリー: 4W6V 7Q0L
• 分子名称: Peptide transporter YePEPT, (2~{S})-2-[[(2~{S})-2-azanyl-6-[(4-nitrophenyl)methoxycarbonylamino]hexanoyl]amino]-3-methyl-butanoic acid, UNDECYL-MALTOSIDE (3 entities in total)
• 機能のキーワード: membrane protein, mfs, peptide transporter, solute transporter, inhibitor bound, lznv, pept1
• 由来する生物種: Yersinia enterocolitica subsp. palearctica YE-P4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57372.83

構造登録者

Jeckelmann, J.M.,Stauffer, M.,Ilgue, H.,Fotiadis, D. (登録日: 2021-10-15, 公開日: 2022-03-09, 最終更新日: 2024-02-07)

主引用文献

Stauffer, M.,Jeckelmann, J.M.,Ilgu, H.,Ucurum, Z.,Boggavarapu, R.,Fotiadis, D.
Peptide transporter structure reveals binding and action mechanism of a potent PEPT1 and PEPT2 inhibitor.
Commun Chem, 5:23-23, 2022

PubMed Abstract: Inhibitors for membrane transporters have been shown to be indispensable as drugs and tool compounds. The proton-dependent oligopeptide transporters PEPT1 and PEPT2 from the SLC15 family play important roles in human and mammalian physiology. With Lys[Z(NO)]-Val (LZNV), a modified Lys-Val dipeptide, a potent transport inhibitor for PEPT1 and PEPT2 is available. Here we present the crystal structure of the peptide transporter YePEPT in complex with LZNV. The structure revealed the molecular interactions for inhibitor binding and a previously undescribed mostly hydrophobic pocket, the PZ pocket, involved in interaction with LZNV. Comparison with a here determined ligand-free structure of the transporter unveiled that the initially absent PZ pocket emerges through conformational changes upon inhibitor binding. The provided biochemical and structural information constitutes an important framework for the mechanistic understanding of inhibitor binding and action in proton-dependent oligopeptide transporters.

PubMed: 36697632
DOI: 10.1038/s42004-022-00636-0

実験手法

X-RAY DIFFRACTION (2.54 Å)