ABCMdb

PMID: 15910875

Matsuo M, Kimura Y, Ueda K
KATP channel interaction with adenine nucleotides.
J Mol Cell Cardiol. 2005 Jun;38(6):907-16. Epub 2005 Feb 5., [PubMed]

Sentences

No. Mutations Sentence Comment

61 ABCC8 p.Lys719Ala ABCC8 p.Asp853Asn Mutations within the Walker A (K719A and K1385M) or Walker B (D853N, D1506A and D1506N) motifs of both NBFs of SUR1 abolished the activation of KATP channels by MgADP [43-45]. Login to comment 74 ABCC8 p.Asp854Asn ABCC8 p.Lys719Met Mutations of either theWalkerA orWalker B motifs of NBF1, K719M and D854N abolished the high-affinity 8-azido-ATP labeling of SUR1, whereas the equivalent mutations in NBF2 did not affect it [47]. Login to comment 82 ABCC8 p.Lys719Ala Gribble et al. [44] reported that mutations in the Walker A motif of both NBFs of SUR1 (K719A and K1385A) abolished the channel activation by MgADP. Login to comment 83 ABCC8 p.Lys719Met We found that the K719M mutation of SUR1 affects 8-azido-ATP binding not only to NBF1 but also to NBF2 (Matsuo M, et al., unpublished data). Login to comment 151 ABCC8 p.Arg1420Cys A missense SUR1 mutation (R1420C) was identified in Japanese PHHI patients [86]. Login to comment 154 ABCC8 p.Arg1420Cys R1420 is located between the Walker A motif and the ABC signature motif of NBF2.An 86 Rb+ efflux study revealed that KATP channels composed of SUR1-R1420C and Kir6.2 are not activated by metabolic inhibition as much as wild-type channels. Login to comment 156 ABCC8 p.Arg1420Cys This may be related to the fact that the expression level of SUR1-R1420C was only about half that of the wild-type channel when it was transiently expressed in COS-7 cells [86]. Login to comment 157 ABCC8 p.Arg1420Cys Photoaffinity labeling experiments revealed that the R1420C PHHI mutation does not affect the affinity of NBF1 for nucleotides, but lowers the affinity of NBF2 for ATP and ADP [88]. Login to comment 158 ABCC8 p.Arg1420Cys The R1420C mutation impairs the cooperative nucleotide binding of two NBFs, although it does not show direct effects on the high-affinity 8-azido-ATP binding to NBF1. Login to comment 161 ABCC8 p.Arg1420Cys Structural modeling of NBFs of SUR1 showed that R1420 is proximal to the a-helical subdomain in NBF2, suggesting that the R1420C mutation affects the interaction of NBFs with nucleotides indirectly [89]. Login to comment 184 ABCC8 p.Ser830Arg ABCC8 p.Ser1446Arg ABCC8 p.Ser1482Arg ABCC7 p.Ser809Arg Mutations within the ABC signature motif of NBF2 of SUR1 (S1482R) and SUR2B (S1446R) abolished the channel activation by MgADP, whereas the corresponding mutation of NBF1 of SUR1 (S830R) and SUR2B (S809R) did not [96]. Login to comment 187 ABCC8 p.Ser1446Arg ABCC7 p.Ser809Arg Interestingly, the serine mutation of NBF1 (S809R) and NBF2 (S1446R) of SUR2A did not affect the channel activation by MgADP [96]. Login to comment