ABCB1 p.Thr581Glu
| Predicted by SNAP2: | A: D (75%), C: D (80%), D: D (91%), E: D (91%), F: D (85%), G: D (85%), H: D (85%), I: D (85%), K: D (91%), L: D (85%), M: D (80%), N: D (85%), P: D (85%), Q: D (85%), R: D (91%), S: D (75%), V: D (85%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, V: D, W: D, Y: D, |
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[hide] Binding of steroid modulators to recombinant cytos... Biochemistry. 1997 Dec 9;36(49):15208-15. Dayan G, Jault JM, Baubichon-Cortay H, Baggetto LG, Renoir JM, Baulieu EE, Gros P, Di Pietro A
Binding of steroid modulators to recombinant cytosolic domain from mouse P-glycoprotein in close proximity to the ATP site.
Biochemistry. 1997 Dec 9;36(49):15208-15., 1997-12-09 [PMID:9398248]
Abstract [show]
We recently found that recombinant NBD1 cytosolic domain corresponding to segment 395-581 of mouse mdr1 P-glycoprotein bound fluorescent 2'(3')-N-methylanthraniloyl-ATP (MANT-ATP) with high affinity [Dayan, G., Baubichon-Cortay, H., Jault, J.-M., Cortay, J. -C., Deleage, G., & Di Pietro, A. (1996) J. Biol. Chem. 271, 11652-11658]. The present work shows that a longer 371-705 domain (extended-NBD1), including tryptophan-696 as an intrinsic probe, which bound MANT-ATP with identical affinity, also interacted with steroids known to modulate anticancer drug efflux from P-glycoprotein-positive multidrug-resistant cells. Progesterone, which is not transported, its hydrophobic derivatives medroxyprogesterone acetate and megestrol acetate, and Delta6-progesterone produced nearly a 50% saturating quenching of the domain intrinsic fluorescence, with dissociation constants ranging from 53 to 18 microM. The even more hydrophobic antiprogestin RU 486 produced a complete quenching of tryptophan-696 fluorescence, in contrast to more hydrophilic derivatives of progesterone containing hydroxyl groups at positions 11, 16, 17, and 21 and known to be transported, which produced very little quenching. A similar differential interaction was observed with full-length purified P-glycoprotein. The steroid-binding region within extended-NBD1 appeared distinct from the nucleotide-binding site as the RU 486-induced quenching was neither prevented nor reversed by high ATP concentrations. In contrast, MANT-ATP binding was efficiently prevented or displaced by RU 486, suggesting that the hydrophobic MANT group of the bound nucleotide analogue overlaps, at least partially, the adjacent steroid-binding region revealed by RU 486.
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No. Sentence Comment
132 In the latter case, it was clearly shown that increasing the C-side extension, from threonine-581 to glutamate-613 or serine-643, gradually lowered the protein solubility during overexpression.
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ABCB1 p.Thr581Glu 9398248:132:84
status: NEW