ABCMdb

PMID: 14593442

Campbell JD, Sansom MS, Ashcroft FM
Potassium channel regulation.
EMBO Rep. 2003 Nov;4(11):1038-42., [PubMed]

Sentences

No. Mutations Sentence Comment

77 ABCC8 p.Asp854Glu Our model suggests that mutation of E1506 in NBD2 to aspartate might reduce ATP hydrolysis, whereas the D854E mutation in site 1 might enhance hydrolytic activity. Login to comment 107 ABCC8 p.Glu1506Lys ABCC8 p.Arg1420Cys ABCC8 p.Leu1551Val ABCC8 p.Gly1381Ser Although some of these mutations prevent targeting of the protein to the plasma membrane, others, such as G1381S, R1420C, E1506K and L1551V (Fig. 3) cause CHI by impairing KATP channel activation in response to metabolic inhibition or MgADP (Huopio et al., 2000). Login to comment 111 ABCC8 p.Leu1551Val In the absence of structural information, it was difficult to envisage why the L1551V mutation abolished KATP channel activation by MgATP and MgADP (Reimann et al., 2003), because in the primary sequence, L1551 is not positioned close to any functionally important conserved motifs. Login to comment 113 ABCC8 p.Gly1381Ser A similar argument can be made for the CHI mutation G1381S, which lies within the WA motif of NBD2, and might therefore influence nucleotide binding at site 2 and so prevent channel activation by MgADP (Shyng et al., 1998). Login to comment 114 ABCC8 p.Arg1420Cys The main effect of the CHI mutation R1420C is to prevent cooperative nucleotide binding (Matsuo et al., 2000b). Login to comment 117 ABCC8 p.Glu1506Lys ABCC8 p.Leu1551Val ABCC8 p.Gly1381Ser Site 1 Site 2 NDB1 NDB2 G1381S E1506K L1551V R1402C Fig. 3 | Location of congenital hyperinsulinism mutations in the nucleotide-binding domains of sulphonylurea receptor SUR1. Login to comment