ABCMdb

ABCC8 p.Lys1384Ala

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Publications

PMID: 16442101 [PubMed] Frelet A et al: "Insight in eukaryotic ABC transporter function by mutation analysis."

No. Sentence Comment

117 In NBD2, K1348M (SUR2B) and K1384A (SUR1) reduced ADP binding [81]. Login to comment

PMID: 11073882 [PubMed] Matsuoka T et al: "C-terminal tails of sulfonylurea receptors control ADP-induced activation and diazoxide modulation of ATP-sensitive K(+) channels."

No. Sentence Comment

106 Effects of Mutations in NBD2 of SUR2B and SUR1 on the ADP and Diazoxide Action Like other ATP-binding cassette proteins, SURs possess 2 nucleotide-binding domains (NBD1 and NBD2, respectively).3 It was shown that SUR1 binds ATP at NBD1 and ADP at NBD2.24 The NBDs possess the Walker A and B motifs to form a portion of a nucleotide-binding pocket.25 In various ATP-binding proteins, Walker A motif in NBDs is responsible for binding or hydrolysis of nucleotides, where the highly conserved lysine residue plays a critical role.26-28 The mutation of this lysine residue in NBD2 extinguishes the ADP-mediated activation of SUR1 and SUR2A-KATP channels.19,21,29 Therefore, we introduced mutations of the lysine residue in NBD2 of SUR2B and SUR1 (K1348M in SUR2B and K1384A in SUR1) and examined the effects of ADP and diazoxide on the mutant SUR/ Kir6.2 channels (Figure 3). Login to comment
110 The mutant SUR1(K1384A)/Kir6.2 channel also scarcely responded to ADP (Figure 3B). Login to comment
111 Different from the SUR2B mutant, diazoxide (30 and 300 ␮mol/L) enhanced the SUR1(K1384A)/ Kir6.2 channel to Ϸ0.1 and Ϸ0.2 in rNPo, respectively, irrespective of [ADP]. Login to comment
114 Effects of intracellular ADP, diazoxide, and pinacidil on SUR2B(K1348M)/ Kir6.2 (A) and SUR1(K1384A)/Kir6.2 (B) channels. Left, Effects of ADP and diazoxide (DZX) or pinacidil (PIN) on SUR2(K1348M)/Kir6.2 and SUR1(K1384A)/ Kir6.2 channels. ATP, ADP, and diazoxide were added to the bath solution as indicated by bars. Right, Relationship between the concentration of ADP and relative NPo (rNPo) in the absence (⅜) and presence of diazoxide (U, 30 ␮mol/L and ⅷ, 300 ␮mol/L) or pinacidil (ᮀ, 100 ␮mol/L). Login to comment
135 In the chimera SUR1-2A/Kir6.2 and the mutant SUR1(K1384A)/Kir6.2 channels, the ADP-dependent component was largely attenuated, and diazoxide (300 ␮mol/L) increased the channel rNPo by Ϸ0.2 irrespective of [ADP]. Login to comment
97 Effects of Mutations in NBD2 of SUR2B and SUR1 on the ADP and Diazoxide Action Like other ATP-binding cassette proteins, SURs possess 2 nucleotide-binding domains (NBD1 and NBD2, respectively).3 It was shown that SUR1 binds ATP at NBD1 and ADP at NBD2.24 The NBDs possess the Walker A and B motifs to form a portion of a nucleotide-binding pocket.25 In various ATP-binding proteins, Walker A motif in NBDs is responsible for binding or hydrolysis of nucleotides, where the highly conserved lysine residue plays a critical role.26-28 The mutation of this lysine residue in NBD2 extinguishes the ADP-mediated activation of SUR1 and SUR2A-KATP channels.19,21,29 Therefore, we introduced mutations of the lysine residue in NBD2 of SUR2B and SUR1 (K1348M in SUR2B and K1384A in SUR1) and examined the effects of ADP and diazoxide on the mutant SUR/ Kir6.2 channels (Figure 3). Login to comment
101 The mutant SUR1(K1384A)/Kir6.2 channel also scarcely responded to ADP (Figure 3B). Login to comment
102 Different from the SUR2B mutant, diazoxide (30 and 300 òe;mol/L) enhanced the SUR1(K1384A)/ Kir6.2 channel to b07;0.1 and b07;0.2 in rNPo, respectively, irrespective of [ADP]. Login to comment
105 Effects of intracellular ADP, diazoxide, and pinacidil on SUR2B(K1348M)/ Kir6.2 (A) and SUR1(K1384A)/Kir6.2 (B) channels. Left, Effects of ADP and diazoxide (DZX) or pinacidil (PIN) on SUR2(K1348M)/Kir6.2 and SUR1(K1384A)/ Kir6.2 channels. ATP, ADP, and diazoxide were added to the bath solution as indicated by bars. Right, Relationship between the concentration of ADP and relative NPo (rNPo) in the absence (Ǧc;) and presence of diazoxide (U, 30 òe;mol/L and ጗, 300 òe;mol/L) or pinacidil (Ⴢ, 100 òe;mol/L). Login to comment
126 In the chimera SUR1-2A/Kir6.2 and the mutant SUR1(K1384A)/Kir6.2 channels, the ADP-dependent component was largely attenuated, and diazoxide (300 òe;mol/L) increased the channel rNPo by b07;0.2 irrespective of [ADP]. Login to comment
96 Effects of Mutations in NBD2 of SUR2B and SUR1 on the ADP and Diazoxide Action Like other ATP-binding cassette proteins, SURs possess 2 nucleotide-binding domains (NBD1 and NBD2, respectively).3 It was shown that SUR1 binds ATP at NBD1 and ADP at NBD2.24 The NBDs possess the Walker A and B motifs to form a portion of a nucleotide-binding pocket.25 In various ATP-binding proteins, Walker A motif in NBDs is responsible for binding or hydrolysis of nucleotides, where the highly conserved lysine residue plays a critical role.26-28 The mutation of this lysine residue in NBD2 extinguishes the ADP-mediated activation of SUR1 and SUR2A-KATP channels.19,21,29 Therefore, we introduced mutations of the lysine residue in NBD2 of SUR2B and SUR1 (K1348M in SUR2B and K1384A in SUR1) and examined the effects of ADP and diazoxide on the mutant SUR/ Kir6.2 channels (Figure 3). Login to comment
100 The mutant SUR1(K1384A)/Kir6.2 channel also scarcely responded to ADP (Figure 3B). Login to comment
104 Effects of intracellular ADP, diazoxide, and pinacidil on SUR2B(K1348M)/ Kir6.2 (A) and SUR1(K1384A)/Kir6.2 (B) channels. Left, Effects of ADP and diazoxide (DZX) or pinacidil (PIN) on SUR2(K1348M)/Kir6.2 and SUR1(K1384A)/ Kir6.2 channels. ATP, ADP, and diazoxide were added to the bath solution as indicated by bars. Right, Relationship between the concentration of ADP and relative NPo (rNPo) in the absence (Ǧc;) and presence of diazoxide (U, 30 òe;mol/L and ጗, 300 òe;mol/L) or pinacidil (Ⴢ, 100 òe;mol/L). Login to comment
125 In the chimera SUR1-2A/Kir6.2 and the mutant SUR1(K1384A)/Kir6.2 channels, the ADP-dependent component was largely attenuated, and diazoxide (300 òe;mol/L) increased the channel rNPo by b07;0.2 irrespective of [ADP]. Login to comment

PMID: 12604678 [PubMed] Chachin M et al: "Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic beta-cell-type K(ATP) channels."

No. Sentence Comment

8 This augmenting effect of MgADP was also observed with the SUR1/Kir6.2(K185Q) channel, which was not inhibited by MgADP, but not with the SUR1(K1384A)/Kir6.2 channel, which was not activated by MgADP. Login to comment
36 SUR1 whose serine at position 1237 was substituted with tyrosine [SUR1(S1237Y)], SUR1 whose lysine at position 1384 was substituted with alanine [SUR1(K1384A)], and Kir6.2 whose lysine at position 185 was substituted with glutamine [Kir6.2(K185Q)] were constructed using the GeneEditor in vitro site-directed mutagenesis system (Promega, Madison, WI). Login to comment
147 To test this hypothesis, we used SUR1 where lysine 1384 in the Walker A motif in nucleotide binding domain 2 was substituted with alanine [SUR1(K1384A)] (Fig. 4C). Login to comment
149 MgADP (100 ␮M) inhibited SUR1(K1384A)/Kir6.2 channels by 58.2 ee; 8.6 and 69.7 Ϯ 5.2% in the absence and presence of nateglinide (10 ␮M), re-Fig. 4. Login to comment
150 Effect of nateglinide on SUR1/Kir6.2(K185Q), SUR1/Kir6.2, and SUR1(K1384A)/Kir6.2 channels in the presence and absence of nucleotides. Login to comment
151 Effects of nateglinide on SUR1/Kir6.2(K185Q) (A), SUR1/Kir6.2 (B), and SUR1(K1384A)/Kir6.2 (C) channel currents were measured in inside-out patches. Login to comment
157 Nateglinide inhibited SUR1(K1384A)/Kir6.2 channel currents by 60.5 Ϯ 6.3 and 71.2 Ϯ 3.8% in the absence and presence of MgADP, respectively (Fig. 4D). Login to comment
146 To test this hypothesis, we used SUR1 where lysine 1384 in the Walker A motif in nucleotide binding domain 2 was substituted with alanine [SUR1(K1384A)] (Fig. 4C). Login to comment
148 MgADP (100 òe;M) inhibited SUR1(K1384A)/Kir6.2 channels by 58.2 afe; 8.6 and 69.7 afe; 5.2% in the absence and presence of nateglinide (10 òe;M), re- Fig. 4. Login to comment
156 Nateglinide inhibited SUR1(K1384A)/Kir6.2 channel currents by 60.5 afe; 6.3 and 71.2 afe; 3.8% in the absence and presence of MgADP, respectively (Fig. 4D). Login to comment