Analysing the substrate multispecificity of a proton-coupled oligopeptide transporter using a dipeptide library
Keisuke Ito (),
Aya Hikida,
Shun Kawai,
Vu Thi Tuyet Lan,
Takayasu Motoyama,
Sayuri Kitagawa,
Yuko Yoshikawa,
Ryuji Kato and
Yasuaki Kawarasaki
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Keisuke Ito: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
Aya Hikida: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
Shun Kawai: Graduate School of Pharmaceutical Sciences, Nagoya University, Furocho
Vu Thi Tuyet Lan: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
Takayasu Motoyama: Food Science Research Institute, Research & Development HQ, Fujioil Co., Ltd.
Sayuri Kitagawa: Food Science Research Institute, Research & Development HQ, Fujioil Co., Ltd.
Yuko Yoshikawa: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
Ryuji Kato: Graduate School of Pharmaceutical Sciences, Nagoya University, Furocho
Yasuaki Kawarasaki: Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
Nature Communications, 2013, vol. 4, issue 1, 1-10
Abstract:
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.
Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3502
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DOI: 10.1038/ncomms3502
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