ABCC8 p.Trp231Ala
| Predicted by SNAP2: | A: D (59%), C: D (53%), D: D (85%), E: D (85%), F: D (75%), G: D (75%), H: D (75%), I: D (75%), K: D (91%), L: D (75%), M: D (75%), N: D (75%), P: D (91%), Q: D (80%), R: D (85%), S: D (66%), T: D (75%), V: D (75%), Y: D (75%), |
| 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, T: D, V: D, Y: D, |
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[hide] Toward linking structure with function in ATP-sens... Diabetes. 2004 Dec;53 Suppl 3:S104-12. Bryan J, Vila-Carriles WH, Zhao G, Babenko AP, Aguilar-Bryan L
Toward linking structure with function in ATP-sensitive K+ channels.
Diabetes. 2004 Dec;53 Suppl 3:S104-12., [PMID:15561897]
Abstract [show]
Advances in understanding the overall structural features of inward rectifiers and ATP-binding cassette (ABC) transporters are providing novel insight into the architecture of ATP-sensitive K+ channels (KATP channels) (KIR6.0/SUR)4. The structure of the K(IR) pore has been modeled on bacterial K+ channels, while the lipid-A exporter, MsbA, provides a template for the MDR-like core of sulfonylurea receptor (SUR)-1. TMD0, an NH2-terminal bundle of five alpha-helices found in SURs, binds to and activates KIR6.0. The adjacent cytoplasmic L0 linker serves a dual function, acting as a tether to link the MDR-like core to the KIR6.2/TMD0 complex and exerting bidirectional control over channel gating via interactions with the NH2-terminus of the KIR. Homology modeling of the SUR1 core offers the possibility of defining the glibenclamide/sulfonylurea binding pocket. Consistent with 30-year-old studies on the pharmacology of hypoglycemic agents, the pocket is bipartite. Elements of the COOH-terminal half of the core recognize a hydrophobic group in glibenclamide, adjacent to the sulfonylurea moiety, to provide selectivity for SUR1, while the benzamido group appears to be in proximity to L0 and the KIR NH2-terminus.
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No. Sentence Comment
162 Results for the wild-type (WT) control, the Tyr230Ala (Y230A), and Trp231Ala (W232A) substitutions are shown.
X
ABCC8 p.Trp231Ala 15561897:162:67
status: NEW