7Q0L

Crystal structure of the peptide transporter YePEPT-K314A at 2.93 A

Summary for 7Q0L

• Entry DOI: 10.2210/pdb7q0l/pdb
• Related: 4W6V
• Descriptor: Peptide transporter YePEPT (1 entity in total)
• Functional Keywords: membrane protein, mfs, peptide transporter, solute transporter
• Biological source: Yersinia enterocolitica subsp. palearctica YE-P4
• Total number of polymer chains: 1
• Total formula weight: 56451.80

Authors

Jeckelmann, J.M.,Stauffer, M.,Ilgue, H.,Boggavarapu, R.,Fotiadis, D. (deposition date: 2021-10-15, release date: 2022-03-09, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.71 Å)