Flavonoid binding to a multi-drug-resistance transporter protein: an STD-NMR study.
Flavonoids are well known to inhibit the function of the multi-drug-resistance (mdr) transporter by interacting with their ATP binding domains. The precise orientation of these molecules inside the ATP binding pocket is still unclear. We applied the saturation transfer difference (STD) NMR technique to investigate the binding of the flavonoid luteolin and its 7-O-beta-D-glycopyranoside to the recombinant nucleotide binding domain (NBD2) of mouse-mdr. First, this NMR technique confirmed binding of both ligands to NBD2, as was determined from tryptophan fluorescence-quenching experiments. Further, the results suggest binding of both luteolin and its 7-O-beta-D-glycopyranoside by their polar groups at positions 4, 5, and 3' to the protein.
Nissler
Ludwig
L
Institute of Biochemistry, Medical Faculty, University of Leipzig, Liebigstrasse 16, 04103 Leipzig, Germany.
Gebhardt
Rolf
R
Berger
Stefan
S
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D004351:Drug Resistance; D008024:Ligands; D047311:Luteolin / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009711:Nucleotides / Q000737:chemistry; D011485:Protein Binding / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012680:Sensitivity and Specificity; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D008024:Ligands; D047311:Luteolin; D009711:Nucleotides; D011994:Recombinant Proteins; D000097202:ATP-Binding Cassette Sub-Family B Member 4