Analysing the substrate multispecificity of a proton-coupled oligopeptide transporter using a dipeptide library.
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.
1] Department of Food and Nutritional Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526, Japan [2] School of Food and Nutritional Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526, Japan [3].
Keisuke
K
Ito
Aya
A
Hikida
Shun
S
Kawai
Vu Thi Tuyet
VT
Lan
Takayasu
T
Motoyama
Sayuri
S
Kitagawa
Yuko
Y
Yoshikawa
Ryuji
R
Kato
Yasuaki
Y
Kawarasaki
D001692:Biological Transport; D004151:Dipeptides / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D011485:Protein Binding; D011522:Protons; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D004151:Dipeptides; D026901:Membrane Transport Proteins; C093495:PTR2 protein, S cerevisiae; D019151:Peptide Library; D011522:Protons; D029701:Saccharomyces cerevisiae Proteins