Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes.

Journal article

Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are a common cause of neonatal diabetes mellitus. Here we investigate the molecular mechanism by which two heterozygous mutations in the second nucleotide-binding domain (NBD2) of SUR1 (R1380L and R1380C) separately cause neonatal diabetes. SUR1 is a channel regulator that modulates the gating of the pore formed by Kir6.2. K(ATP) channel activity is inhibited...

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Authors: De Wet, H; Rees, MG; Shimomura, K; Aittoniemi, J; Patch, A

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 104
• Issue: 48
• Pages: 18988-18992
• Publication date: 2007-11-01
• DOI: 10.1073/pnas.0707428104
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Fluorides; Potassium Channels, Inwardly Rectifying; Ion Channel Gating; Adenosine Triphosphate; Models, Molecular; Diabetes Mellitus, Type 1; Potassium Channels; Point Mutation; Beryllium; Mutation, Missense; Protein Structure, Tertiary; Binding Sites; Arginine; Amino Acid Substitution; ATP-Binding Cassette Transporters; Infant, Newborn; Potassium; Structure-Activity Relationship; Insulin; Kinetics; Humans; Hydrolysis; Adenosine Diphosphate; Receptors, Drug