ABCB1 p.Leu332Val
| Predicted by SNAP2: | A: D (59%), C: N (53%), D: D (85%), E: D (80%), F: N (53%), G: D (80%), H: D (80%), I: N (82%), K: D (85%), M: N (87%), N: D (75%), P: D (85%), Q: D (71%), R: D (80%), S: D (71%), T: D (63%), V: N (57%), W: D (66%), Y: D (71%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Inhibition of oxidative cross-linking between engi... J Biol Chem. 1996 Nov 1;271(44):27482-7. Loo TW, Clarke DM
Inhibition of oxidative cross-linking between engineered cysteine residues at positions 332 in predicted transmembrane segments (TM) 6 and 975 in predicted TM12 of human P-glycoprotein by drug substrates.
J Biol Chem. 1996 Nov 1;271(44):27482-7., 1996-11-01 [PMID:8910331]
Abstract [show]
Each homologous half of P-glycoprotein consists of a transmembrane domain with six potential transmembrane segments and an ATP-binding domain. Labeling studies with photoactive drug analogs show that labeling occurs within or close to predicted transmembrane segments (TM) 6 (residues 331-351) and TM12 (residues 974-994). To test if these segments are in near-proximity we generated 42 different P-glycoprotein mutants in which we re-introduced a pair of cysteine residues into a Cys-less P-glycoprotein, one within TM6 (residues 332-338) and one within TM12 (residues 975-980) and assayed for cross-linking between the cysteines. All the mutants retained verapamil-stimulated ATPase activity. We found that only the mutant containing Cys-332 and Cys-975 was cross-linked in the presence of oxidant as judged by its decreased mobility on SDS gels. Similar results were obtained when the same mutations were introduced into Cys-less NH2-terminal and COOH-terminal half-molecules of P-glycoprotein followed by coexpression and treatment with oxidant. Cross-linking between Cys-332 and Cys-975, however, was inhibited by verapamil or vinblastine but not by colchicine. These results suggest that residues Cys-332 and Cys-975, which occupy equivalent positions when TM6 and TM12 are aligned, are close to each other in the tertiary structure of P-glycoprotein.
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No. Sentence Comment
138 Each residue at equivalent positions in predicted TM6 (residues Leu-332-Val-338) and TM11 (residues Met-949-Cys-956) was systematically changed to cysteine followed by treatment of the protein with oxidant.
X
ABCB1 p.Leu332Val 8910331:138:64
status: NEW