ABCMdb

PMID: 8548288

Sullivan SK, Agellon LB, Schick R
Identification and partial characterization of a domain in CFTR that may bind cyclic nucleotides directly.
Curr Biol. 1995 Oct 1;5(10):1159-67., [PubMed]

Sentences

No. Mutations Sentence Comment

124 ABCC7 p.Thr421Ala ABCC7 p.Glu407Gln ABCC7 p.Glu407Gln ABCC7 p.Leu408Ala The current was only 18 + 13 % (n = 3) of wild-type level for the mutant channel with the glutamate at position 407 substituted by glutamine (mutant E407Q, using the single-letter amino-acid code); 16 + 3 % (n = 4) for the L408A mutant; and 17 &#b1;+1 % (n = 4) for the T421A mutant (data not shown). Login to comment 125 ABCC7 p.Thr421Ala ABCC7 p.Glu407Gln ABCC7 p.Glu407Gln ABCC7 p.Leu408Ala The current was only 18 + 13 % (n = 3) of wild-type level for the mutant channel with the glutamate at position 407 substituted by glutamine (mutant E407Q, using the single-letter amino-acid code); 16 + 3 % (n = 4) for the L408A mutant; and 17 ±+1 % (n = 4) for the T421A mutant (data not shown). Login to comment 126 ABCC7 p.Glu403Asp ABCC7 p.Glu407Gln A double substitution mutant (E407Q plus E403D) produced 63 + 8 % (n = 9) wild-type channel current (wild-type =2250 + 195 nA; n = 5; data not shown). Login to comment 127 ABCC7 p.Glu403Asp ABCC7 p.Glu407Gln A double substitution mutant (E407Q plus E403D) produced 63 + 8 % (n = 9) wild-type channel current (wild-type =2250 + 195 nA; n = 5; data not shown). Login to comment 132 ABCC7 p.Gly406Ala The G406A mutant responded normally to cGMP (Fig. 7a,c). Login to comment 133 ABCC7 p.Gly406Ala The G406A mutant responded normally to cGMP (Fig. 7a,c). Login to comment 134 ABCC7 p.Val397Ala The V397A mutant displayed a cGMP response that was enhanced by 66 + 19 % (n = 5; p < 0.05) relative to the wild-type channel (Fig. 7a,b). Login to comment 135 ABCC7 p.Val397Ala ABCC7 p.Lys420Ala The V397A mutant displayed a cGMP response that was enhanced by 66 + 19 % (n = 5; p < 0.05) relative to the wild-type channel (Fig. 7a,b). Login to comment 136 ABCC7 p.Lys420Ala The K420A substitution, which produced the largest effect, reduced the cGMP response by 75 ± 6 % (n = 4; p < 0.005; Fig. 7a,c) compared with the wild-type channel. Login to comment 147 ABCC7 p.Val397Ala (b) Effect of V397A substitution compared with the wild-type CFTR (n = 5). Login to comment 148 ABCC7 p.Gly406Ala ABCC7 p.Val397Ala ABCC7 p.Lys420Ala (b) Effect of V397A substitution compared with the wild-type CFTR (n = 5). Login to comment 149 ABCC7 p.Gly406Ala ABCC7 p.Lys420Ala (c) Effect of G406A or K420A substitutions compared with wild-type CFTR (n= 4). Login to comment 151 ABCC7 p.Gly406Ala ABCC7 p.Val397Ala ABCC7 p.Lys420Ala The three other single-substitution mutants (V397A, G406A and K420A) produced functional channels that responded to cAMP in a manner identical to wild type, Direct activation may also be modulated by phosphorylation. Login to comment 152 ABCC7 p.Gly406Ala ABCC7 p.Val397Ala ABCC7 p.Lys420Ala The three other single-substitution mutants (V397A, G406A and K420A) produced functional channels that responded to cAMP in a manner identical to wild type, Direct activation may also be modulated by phosphorylation. Login to comment 174 ABCC7 p.Gly406Ala The substitution of an alanine for the glycine at position 406, which replaced the minimal proton with a bulkier methyl group, had no effect on activation by cGMP As this glycine is invariant, the substitution was predicted to be disruptive. Login to comment 175 ABCC7 p.Gly406Ala The substitution of an alanine for the glycine at position 406, which replaced the minimal proton with a bulkier methyl group, had no effect on activation by cGMP As this glycine is invariant, the substitution was predicted to be disruptive. Login to comment 177 ABCC7 p.Lys420Ala The substitution of an alanine for the lysine at position 420 was predicted to disrupt an ionic interaction with exocyclic phosphate oxygen, resulting in reduced activation by cGMP. Login to comment 178 ABCC7 p.Lys420Ala The substitution of an alanine for the lysine at position 420 was predicted to disrupt an ionic interaction with exocyclic phosphate oxygen, resulting in reduced activation by cGMP. Login to comment