ABCC8 p.Asp1512Ala
| Predicted by SNAP2: | A: D (91%), C: D (91%), E: D (66%), F: D (91%), G: D (91%), H: D (85%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), N: D (91%), P: D (95%), Q: D (91%), R: D (95%), S: D (91%), T: D (91%), V: D (91%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | A: D, C: 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, W: D, Y: D, |
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[hide] Identification of a functionally important negativ... Diabetes. 2004 Dec;53 Suppl 3:S123-7. Campbell JD, Proks P, Lippiat JD, Sansom MS, Ashcroft FM
Identification of a functionally important negatively charged residue within the second catalytic site of the SUR1 nucleotide-binding domains.
Diabetes. 2004 Dec;53 Suppl 3:S123-7., [PMID:15561899]
Abstract [show]
The ATP-sensitive K+ channel (KATP channel) couples glucose metabolism to insulin secretion in pancreatic beta-cells. It is comprised of sulfonylurea receptor (SUR)-1 and Kir6.2 proteins. Binding of Mg nucleotides to the nucleotide-binding domains (NBDs) of SUR1 stimulates channel opening and leads to membrane hyperpolarization and inhibition of insulin secretion. To elucidate the structural basis of this regulation, we constructed a molecular model of the NBDs of SUR1, based on the crystal structures of mammalian proteins that belong to the same family of ATP-binding cassette transporter proteins. This model is a dimer in which there are two nucleotide-binding sites, each of which contains residues from NBD1 as well as from NBD2. It makes the novel prediction that residue D860 in NBD1 helps coordinate Mg nucleotides at site 2. We tested this prediction experimentally and found that, unlike wild-type channels, channels containing the SUR1-D860A mutation were not activated by MgADP in either the presence or absence of MgATP. Our model should be useful for designing experiments aimed at elucidating the relationship between the structure and function of the KATP channel.
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No. Sentence Comment
85 The equivalent mutation in NBD2 of SUR1 (D1512A) did not result in functional channels.
X
ABCC8 p.Asp1512Ala 15561899:85:41
status: NEW