ABCB1 p.Gln1280Ala
| Predicted by SNAP2: | A: N (82%), C: N (72%), D: N (82%), E: N (93%), F: N (78%), G: N (78%), H: N (93%), I: N (82%), K: N (97%), L: N (82%), M: N (87%), N: N (87%), P: N (72%), R: N (97%), S: N (87%), T: N (87%), V: N (82%), W: N (61%), Y: N (82%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] P-glycoprotein function involves conformational tr... Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12908-13. Mechetner EB, Schott B, Morse BS, Stein WD, Druley T, Davis KA, Tsuruo T, Roninson IB
P-glycoprotein function involves conformational transitions detectable by differential immunoreactivity.
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12908-13., 1997-11-25 [PMID:9371774]
Abstract [show]
The MDR1 P-glycoprotein (Pgp), a member of the ATP-binding cassette family of transporters, is a transmembrane ATPase efflux pump for various lipophilic compounds, including many anti-cancer drugs. mAb UIC2, reactive with the extracellular moiety of Pgp, inhibits Pgp-mediated efflux. UIC2 reactivity with Pgp was increased by the addition of several Pgp-transported compounds or ATP-depleting agents, and by mutational inactivation of both nucleotide-binding domains (NBDs) of Pgp. UIC2 binding to Pgp mutated in both NBDs was unaffected in the presence of Pgp transport substrates or in ATP-depleted cells, whereas the reactivities of the wild-type Pgp and Pgps mutated in a single NBD were increased by these treatments to the level of the double mutant. These results indicate the existence of different Pgp conformations associated with different stages of transport-associated ATP hydrolysis and suggest trapping in a transient conformation as a mechanism for antibody-mediated inhibition of Pgp.
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No. Sentence Comment
22 The mutant Pgps contain K433M and͞or K1076M substitutions in the Walker A motifs; in addition, the cloning procedure resulted in a Q1280A substitution of the C-terminal amino acid in all of the transfected MDR1 cDNA sequences.
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ABCB1 p.Gln1280Ala 9371774:22:137
status: NEW