Analysing the Substrate Multispecificity of a Proton-coupled Oligopeptide Transporter Using a Dipeptide Library

Overview

Journal Nat Commun

Specialty Biology

Date 2013 Sep 25

PMID 24060756

Citations 24

Authors

Keisuke Ito

Aya Hikida

Shun Kawai

Vu Thi Tuyet Lan

Takayasu Motoyama

Sayuri Kitagawa

Yuko Yoshikawa

Ryuji Kato

Yasuaki Kawarasaki

Affiliations

Soon will be listed here.

Abstract

Peptide uptake systems that involve members of the proton-coupled oligopeptide transporter (POT) family are conserved across all organisms. POT proteins have characteristic substrate multispecificity, with which one transporter can recognize as many as 8,400 types of di/tripeptides and certain peptide-like drugs. Here we characterize the substrate multispecificity of Ptr2p, a major peptide transporter of Saccharomyces cerevisiae, using a dipeptide library. The affinities (Ki) of di/tripeptides toward Ptr2p show a wide distribution range from 48 mM to 0.020 mM. This substrate multispecificity indicates that POT family members have an important role in the preferential uptake of vital amino acids. In addition, we successfully establish high performance ligand affinity prediction models (97% accuracy) using our comprehensive dipeptide screening data in conjunction with simple property indices for describing ligand molecules. Our results provide an important clue to the development of highly absorbable peptides and their derivatives including peptide-like drugs.

Citing Articles

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Parker J, Deme J, Lichtinger S, Kuteyi G, Biggin P, Lea S Nat Commun. 2024; 15(1):8755.

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Structural basis for antibiotic transport and inhibition in PepT2, the mammalian proton-coupled peptide transporter.

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