ABCMdb

ABCC7 p.Lys978Pro

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Publications

PMID: 23620589 [PubMed] Okeyo G et al: "Converting nonhydrolyzable nucleotides to strong cystic fibrosis transmembrane conductance regulator (CFTR) agonists by gain of function (GOF) mutations."

No. Sentence Comment

104 Accordingly, we compared the activation by AMP-PNP of several previously described GOF CFTR mutants with increasing degrees of unliganded activity (K978P, K978C, and K190C/K978C; see Fig. 3). Login to comment
105 All three GOF mutants were more strongly activated by AMP-PNP than WT-CFTR, with the lowest and greatest relative activation observed for the weakest (K978P; Fig. 3, A, C, and D) and strongest (K190C/K978C; Fig. 3, B, C, and D) GOF mutant. Login to comment
155 Fig. 5, C and D, show that the AMP-PNP-activated currents mediated by K978P-CFTR were strongly but slowly inhibited by diamide/GSH (inactivation time constant b0e;1 min). Login to comment
157 K978P-CFTR channels lacking Cys-1344 were insensitive to diamide/GSH (Fig. 5D, supplemental Fig. S2), as we observed previously for channels without the GOF mutation (27). Login to comment
158 The slow rate of K978P-CFTR inactivation by diamide/GSH is consistent with the idea that AMP-PNP binds tightly at the NBD dimer interface and restricts access of the reactive glutathione to Cys-1344 (27). Login to comment
169 A and B, representative macropatch records show AMP-PNP activation of K978P-CFTR (A) and K190C/K978C-CFTR (B). Login to comment
220 D, mean inhibition by diamide/glutathione of the AMP-PNP activated currents for K978P-CFTR (n afd; 5) and K978P/C1344A- CFTR (n afd; 3) is shown. Login to comment
259 In this regard, the substitutions at position Lys-978 that had the strongest GOF effects (K978C, K978S, and K978P; Ref. 13) also are predicted to have the greatest disruptive effects on the presumed helical structure of cytosolic loop3 and TM9 based on secondary structure predictions (results not shown). Login to comment