RRC ID |
61153
|
著者 |
Yamashiro T, Yasujima T, Ohta K, Inoue K, Yuasa H.
|
タイトル |
Identification of the amino acid residue responsible for the myricetin sensitivity of human proton-coupled folate transporter.
|
ジャーナル |
Sci Rep
|
Abstract |
Human proton-coupled folate transporter (hPCFT/SLC46A1) has recently been found to be inhibited by myricetin by a sustained mechanism, raising a concern that the inhibition might lead to malabsorption of folates in the intestine, where hPCFT works for their epithelial uptake. However, rat PCFT (rPCFT) has more recently been found not to be inhibited by myricetin. Prompted by this finding, we attempted to determine the amino acid residue involved in that by analyses comparing between hPCFT and rPCFT. In the initial analysis, chimeric constructs prepared from hPCFT and rPCFT were examined for myricetin sensitivity to determine the hPCFT segment involved in the sensitivity. Focusing on the thereby determined segment from 83rd to 186th amino acid residue, hPCFT mutants having a designated amino acid residue replaced with its counterpart in rPCFT were prepared for the subsequent analysis. Among them, only G158N-substituted hPCFT was found to be transformed to be insensitive to myricetin and, accordingly, oppositely N158G-substituted rPCFT was transformed to be sensitive to myricetin. These results indicate the critical role of Gly158 in the myricetin sensitivity of hPCFT. This finding would help advance the elucidation of the mechanism of the myricetin-induced inhibition of hPCFT and manage the potential risk arising from that.
|
巻・号 |
9(1)
|
ページ |
18105
|
公開日 |
2019-12-2
|
DOI |
10.1038/s41598-019-54367-9
|
PII |
10.1038/s41598-019-54367-9
|
PMID |
31792273
|
PMC |
PMC6889420
|
MeSH |
Amino Acid Substitution
Flavonoids / pharmacology*
Folic Acid / pharmacokinetics
Glycine / genetics*
HEK293 Cells
Humans
Intestinal Absorption / drug effects
Intestinal Absorption / physiology
Mutagenesis, Site-Directed
Proton-Coupled Folate Transporter / genetics*
Proton-Coupled Folate Transporter / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
|
IF |
3.998
|
リソース情報 |
遺伝子材料 |
pCI-neo-bPCFT (RDB18233)
pCI-neo-mPCFT (RDB18234)
pCI-neo-agmPCFT (RDB18232) |
ヒト・動物細胞 |
MDBK(RCB0180)
RAW 264(RCB0535) |