Peptide transporter structure reveals binding and action mechanism of a potent PEPT1 and PEPT2 inhibitor

Abstract

Understanding the molecular interactions between proton-dependent oligopeptide transporters and their inhibitors is key to drug and tool development, but high-resolution co-crystal structure data remains scarce. Here, the authors report the crystal structure of YePEPT-K314A in complex with the potent inhibitor Lys[Z(NO2)]-Val, revealing the molecular interactions involved in inhibitor binding and a previously undescribed hydrophobic pocket.