ABCC8 p.Ile1254Val
| Predicted by SNAP2: | A: D (66%), C: N (53%), D: D (85%), E: D (85%), F: D (66%), G: D (85%), H: D (85%), K: D (85%), L: N (87%), M: N (66%), N: D (85%), P: D (91%), Q: D (80%), R: D (85%), S: D (80%), T: D (71%), V: N (87%), W: D (85%), Y: D (80%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, K: D, L: N, 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] The molecular basis of the specificity of action o... EMBO J. 2000 Dec 15;19(24):6644-51. Moreau C, Jacquet H, Prost AL, D'hahan N, Vivaudou M
The molecular basis of the specificity of action of K(ATP) channel openers.
EMBO J. 2000 Dec 15;19(24):6644-51., [PMID:11118199]
Abstract [show]
K(ATP) channels incorporate a regulatory subunit of the ATP-binding cassette (ABC) transporter family, the sulfonylurea receptor (SUR), which defines their pharmacology. The therapeutically important K(+) channel openers (e.g. pinacidil, cromakalim, nicorandil) act specifically on the SUR2 muscle isoforms but, except for diazoxide, remain ineffective on the SUR1 neuronal/pancreatic isoform. This SUR1/2 dichotomy underpinned a chimeric strategy designed to identify the structural determinants of opener action, which led to a minimal set of two residues within the last transmembrane helix of SUR. Transfer of either residue from SUR2A to SUR1 conferred opener sensitivity to SUR1, while the reverse operation abolished SUR2A sensitivity. It is therefore likely that these residues form part of the site of interaction of openers with the channel. Thus, openers would target a region that, in other ABC transporters, is known to be tightly involved with the binding of substrates and other ligands. This first glimpse of the site of action of pharmacological openers should permit rapid progress towards understanding the structural determinants of their affinity and specificity.
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No. Sentence Comment
60 Within helix H17, L1249 and T1253 were most closely linked to opener activation since mutant SUR2A(L1249T,T1253M) became almost immune to activation, but mutant SUR2A(I1254V,T1255S) kept a wild-type phenotype.
X
ABCC8 p.Ile1254Val 11118199:60:167
status: NEW59 Within helix H17, L1249 and T1253 were most closely linked to opener activation since mutant SUR2A(L1249T,T1253M) became almost immune to activation, but mutant SUR2A(I1254V,T1255S) kept a wild-type phenotype.
X
ABCC8 p.Ile1254Val 11118199:59:167
status: NEW