Seed and vascular expression of a high-affinity transporter for cationic amino acids in Arabidopsis.

AbstractSince 3000 B.C., evergreen plant Thea sinensis (Theaceae) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

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Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs

Nucleic Acids Research ◽

10.1093/nar/gkab041 ◽

2021 ◽

Author(s):

Amit Ketkar ◽

Lane Smith ◽

Callie Johnson ◽

Alyssa Richey ◽

Makayla Berry ◽

...

Keyword(s):

Amino Acids ◽

Mutation Frequency ◽

Control Sequence ◽

Wild Type ◽

Binding Properties ◽

High Affinity ◽

G4 Dna ◽

G Quadruplex ◽

Forward Mutagenesis

Abstract We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency >200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased >700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication.

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The two-way flux of cationic amino acids across the plasma membrane of mammalian cells is largely explained by a single transport system.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)33986-3 ◽

1982 ◽

Vol 257 (17) ◽

pp. 10069-10080 ◽

Cited By ~ 9

Author(s):

M F White ◽

H N Christensen

Keyword(s):

Amino Acids ◽

Plasma Membrane ◽

Transport System ◽

Mammalian Cells ◽

Cationic Amino Acids

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Cloning and characterization of a human brain Na + -independent transporter for small neutral amino acids that transports d -serine with high affinity

Neuroscience Letters ◽

10.1016/s0304-3940(00)01169-1 ◽

2000 ◽

Vol 287 (3) ◽

pp. 231-235 ◽

Cited By ~ 77

Author(s):

Jun Nakauchi ◽

Hirotaka Matsuo ◽

Do Kyung Kim ◽

Akiteru Goto ◽

Arthit Chairoungdua ◽

...

Keyword(s):

Amino Acids ◽

Human Brain ◽

Neutral Amino Acids ◽

High Affinity

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Differential inhibitory action of cationic amino acids on protein synthesis in pancreatic rat islets

Diabetologia ◽

10.1007/bf00290592 ◽

1988 ◽

Vol 31 (4) ◽

pp. 241-246

Author(s):

C. Patzelt

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Inhibitory Action ◽

Rat Islets ◽

Cationic Amino Acids

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Expression cloning of a human renal cDNA that induces high affinity transport of L-cystine shared with dibasic amino acids in Xenopus oocytes

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)82410-3 ◽

1993 ◽

Vol 268 (20) ◽

pp. 14842-14849

Author(s):

J. Bertran ◽

A. Werner ◽

J. Chillarón ◽

V. Nunes ◽

J. Biber ◽

...

Keyword(s):

Amino Acids ◽

Xenopus Oocytes ◽

Expression Cloning ◽

High Affinity ◽

Dibasic Amino Acids

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Single amino acid substitution of rat MRP2 results in acquired transport activity for taurocholate

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.281.4.g1034 ◽

2001 ◽

Vol 281 (4) ◽

pp. G1034-G1043 ◽

Cited By ~ 31

Author(s):

Kousei Ito ◽

Hiroshi Suzuki ◽

Yuichi Sugiyama

Keyword(s):

Amino Acids ◽

Multidrug Resistance ◽

Amino Acid ◽

Membrane Vesicles ◽

Single Amino Acid ◽

Sf9 Cells ◽

Transport Activity ◽

Wild Type ◽

Cationic Amino Acids ◽

The Difference

Multidrug resistance-associated protein 3 (MRP3), unlike other MRPs, transports taurocholate (TC). The difference in TC transport activity between rat MRP2 and MRP3 was studied, focusing on the cationic amino acids in the transmembrane domains. For analysis, transport into membrane vesicles from Sf9 cells expressing wild-type and mutated MRP2 was examined. Substitution of Arg at position 586 with Leu and Ile and substitution of Arg at position 1096 with Lys, Leu, and Met resulted in the acquisition of TC transport activity, while retaining transport activity for glutathione and glucuronide conjugates. Substitution of Leu at position 1084 of rat MRP3 (which corresponds to Arg-1096 in rat MRP2) with Lys, but not with Val or Met, resulted in the loss of transport activity for TC and glucuronide conjugates. These results suggest that the presence of the cationic charge at Arg-586 and Arg-1096 in rat MRP2 prevents the transport of TC, whereas the presence of neutral amino acids at the corresponding position of rat MRP3 is required for the transport of substrates.

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