Proton-dependent oligopeptide transporter (POT) (POT)

Bacterial peptide/organic cation transporters, primarily represented by the Proton-dependent Oligopeptide Transporter (POT) family (also known as the PTR family), are integral membrane proteins that facilitate the uptake of di- and tri-peptides from the extracellular environment into the bacterial cytoplasm [2]. These transporters are members of the Major Facilitator Superfamily (MFS) and function as symporters, utilizing the inward-directed proton electrochemical gradient (proton motive force) to drive substrate transport [2, 10]. Beyond their physiological role in nutrient acquisition and nitrogen metabolism, these transporters are of significant pharmacological interest because they can recognize and transport a wide variety of peptidomimetic drugs, including beta-lactam antibiotics like cephalosporins (e.g., cephalexin, cefadroxil) and various peptide-conjugated prodrugs [2, 11]. By hijacking these nutrient uptake pathways, these drugs can achieve high intracellular concentrations, which is essential for their antimicrobial efficacy [2]. The study of bacterial POTs, such as DtpA from Escherichia coli, has provided critical structural and functional insights into the mechanism of peptide transport, serving as a model for understanding human homologs like PEPT1 and PEPT2 [6, 10]. Consequently, these transporters are considered important targets for improving drug delivery and overcoming certain types of bacterial resistance [2, 11].

Other names

Peptide transport (PTR) familyBacterial peptide/organic cation transportersDi- and tripeptide permeaseDtp familySLC15 homologsProton-coupled oligopeptide transporter

Facilitated uptake of peptidomimetic drugs via proton-coupled symport