ABCC8 p.Ser1185Ala
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PMID: 22451668
[PubMed]
Ortiz D et al: "Two neonatal diabetes mutations on transmembrane helix 15 of SUR1 increase affinity for ATP and ADP at nucleotide binding domain 2."
No.
Sentence
Comment
48
These substitutions are in a cluster of mutations that cause either neonatal diabetes (Q1178R, R1182Q, and A1184E) or hyperinsulinism (C1174F and S1185A).
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ABCC8 p.Ser1185Ala 22451668:48:146
status: NEW
PMID: 25926814
[PubMed]
Ortiz D et al: "Neonatal Diabetes and Congenital Hyperinsulinism Caused by Mutations in ABCC8/SUR1 are Associated with Altered and Opposite Affinities for ATP and ADP."
No.
Sentence
Comment
122
to the current regulatory model, both E1506 substitutions have reduced affinity for MgADP (Figure 4), consistent with electrophysiological data demonstrating that SUR1E1506D/Kir6.2 and 10 -1 10 0 10 1 10 2 10 3 10 4 10 5 0.0 0.2 0.4 0.6 0.8 1.0 E1506Q Q1178R E1506D R1182Q I1424V WT S1185A C1174F E1506K G1479R Specific Bound GBC [MgATP] (&#b5;M) 10 -1 10 0 10 1 10 2 10 3 10 4 10 5 0.0 0.2 0.4 0.6 0.8 1.0 E1506Q E1506K Q1178R I1424V E1506D R1182Q WT S1185A C1174F G1479R Specific Bound GBC [ATP 4- ] (&#b5;M) B A FIGURE 3 | Comparison of nucleotide-induced conformational switching in WT and SUR1 mutants.
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ABCC8 p.Ser1185Ala 25926814:122:283
status: NEWX
ABCC8 p.Ser1185Ala 25926814:122:452
status: NEW128 To support this hypothesis we analyzed additional mutations including I1424V (ND) and G1479R (CHI) in NBD2 and a cluster of disease causing mutations in TMD2: C1174F (CHI), S1185A (CHI), Q1178R (ND), and R1182Q (ND).
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ABCC8 p.Ser1185Ala 25926814:128:173
status: NEW151 Figure 5 shows that diazoxide potentiates the 1 10 100 1000 0.0 0.2 0.4 0.6 0.8 1.0 Q1178R I1424V R1182Q S1185A C1174F WT E1506Q E1506D G1479R E1506K Specific Bound GBC [MgADP] (&#b5;M) FIGURE 4 | MgADP-induced conformational switching in WT and SUR1 mutants.
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ABCC8 p.Ser1185Ala 25926814:151:105
status: NEW152 10 100 1 0.0 0.2 0.4 0.6 0.8 1.0 1 10 100 0.0 0.2 0.4 0.6 0.8 1.0 WT S1185A C1174F G1479R Specific Bound GBC [Diazoxide] (&#b5;M) Specific Bound GBC [Diazoxide] (&#b5;'c;) FIGURE 5 | Diazoxide potentiates conformational switching in WT and CHI SUR1 mutants.
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ABCC8 p.Ser1185Ala 25926814:152:69
status: NEW