ABCMdb

ABCC7 p.Cys1344Ala

None has been submitted yet.

Publications

PMID: 15657297 [PubMed] Wang W et al: "Reversible silencing of CFTR chloride channels by glutathionylation."

No. Sentence Comment

169 All CFTR constructs, with the exception of C1344A-CFTR, were markedly inhibited by diamide/GSH (Fig. 7, B and C). Login to comment
170 C1344A-CFTR was largely, although not completely, resistant to each of the three glutathione species at the indicated concentrations (Fig. 7, B and D). Login to comment
212 CFTR channels that lack cys-1344 (C1344A-CFTR) are largely resistant to inhibition by reactive glutathione species. Login to comment
219 (C) Representative current trace showing resistance of C1344A-CFTR to inhibition by diamide/GSH. Login to comment
220 (D) Mean data comparing the sensitivities of WT CFTR and C1344A-CFTR to inhibition by diamide/ GSH (20 ␮M), GSNO (200 ␮M), and GSSG (20 mM). Login to comment
227 However, the fact that C1344A-CFTR was the only cysteine mutant that was highly resistant to inhibition by all three reactive glutathione species (GSNO, GSSG, and diamide/GSH) indicates that this cysteine likely is the functionally important site for glutathionylation. Login to comment

PMID: 20974851 [PubMed] Melani R et al: "Modulation of cystic fibrosis transmembrane conductance regulator (CFTR) activity and genistein binding by cytosolic pH."

No. Sentence Comment

42 EXPERIMENTAL PROCEDURES Cell Culture-Fisher rat thyroid (FRT) cells stably transfected with WT-CFTR or with CFTR carrying the C491A or C1344A mutation were grown as described previously (23). Login to comment
75 Both C491A and C1344A were produced on a wild-type CFTR background. Login to comment
87 Genistein Potentiation of C1344A-CFTR Maintains the Sensitivity to pH 8-The cysteine mutant outside the putative binding site for potentiators, C1344A, showed a CPT-cAMP maximum current even smaller than C491A, but the equilibrium constant (Kd) was very close to the equilibrium constants of C491A and WT-CFTR (Table 1). Login to comment
88 Similar to the other two proteins, also C1344A-CFTR showed a higher apparent affinity (lower Kd) for CPT-cAMP at pH 6. Login to comment
100 Parameter pH 6.0 7.35 8.0 Im (␮A⅐cm-2 ) WT 127.7 Ϯ 15.8 (10)a 185.5 Ϯ 17.3 (23) 231.8 Ϯ 27.4 (14) C491A 13.9 Ϯ 3.7 (9)a 36.1 Ϯ 4.5 (8) 29.9 Ϯ 2.2 (8) C1344A 2.2 Ϯ 0.5 (5)a 6.2 Ϯ 1.7 (9) 11.7 Ϯ 2.2 (8) Kd (␮M) WT 32.7 Ϯ 6 (10)a 56.6 Ϯ 5.9 (23) 71.9 Ϯ 13.3 (14) C491A 10.3 Ϯ 1.2 (9)a 56.7 Ϯ 6.2 (8) 67.7 Ϯ 8.6 (9) C1344A 11.2 Ϯ 2 (5)a 63.4 Ϯ 9.4 (9) 104.3 Ϯ 12.7 (8) a p Ͻ 0.05 compared with the same parameter on the same protein at pH 7.35. Login to comment
102 Parameter pH 6 7.35 8.0 fA WT 1.24 Ϯ 0.22 (12) 1.87 Ϯ 0.34 (14) 4.36 Ϯ 0.83 (16)a C491A 2.57 Ϯ 0.58 (11) 3.29 Ϯ 0.53 (13) 3.85 Ϯ 0.54 (11) C1344A 1.84 Ϯ 0.64 (4) 4.5 Ϯ 1.2 (9) 5.23 Ϯ 0.89 (13) Ka (␮M) WT 1.83 Ϯ 0.43 (12) 1.81 Ϯ 0.37 (14) 4.99 Ϯ 0.89 (16)a C491A 17.2 Ϯ 4 (11) 17.8 Ϯ 5.44 (13) 16.4 Ϯ 3.29 (11) C1344A 8.2 Ϯ 1.27 (4) 10.1 Ϯ 2.17 (9) 20 Ϯ 3.53 (13)a Ki (␮M) WT 250.9 Ϯ 29.5 (12) 368 Ϯ 50.9 (14) 237.9 Ϯ 44.95 (16) C491A 78.5 Ϯ 21.2 (11) 108.5 Ϯ 24.3 (13) 394.9 Ϯ 70.4 (12)a C1344A 23.8 Ϯ 2.48 (4)a 73.9 Ϯ 12.7 (9) 398.75 Ϯ 87.1 (13)a a p Ͻ 0.05 compared with the same parameter at pH 7.35 on the same protein. Login to comment
104 The Ka was found to be higher than that of the WT-CFTR, but as in the WT channel, the Ka of C1344A-CFTR increased when pHi was set at a value of 8. Login to comment
105 This indicates that, in contrast to what was found with C491A, the C1344A mutation did not modify the sensitivity of genistein binding to the activating site at alkaline pHi (Fig. 3C). Login to comment
120 A, Western blot showing CFTR protein expression in untransfected FRT cells (FRT-null) and in cells stably transfected with WT-, C491A-, and C1344A-CFTR. Login to comment
131 Dose-response relationship of C1344A-CFTR to genistein. Login to comment
132 A, representative traces showing the response of mutant C1344A-CFTR to increasing doses of genistein (indicated by arrows). Login to comment
133 Dashed lines under the curves indicate the zero current level. B, normalized dose-response relationships in experiments on mutant C1344A at pH 6 (n ϭ 4), 7.35 (n ϭ 4), and 8 (n ϭ 4). Login to comment
134 C, course of Ka measured on WT-, C491A-, and C1344A-CFTR at different pHi values. Login to comment
138 However, at pHi 8, the Ka for WT and C1344A-CFTR increased significantly (p Ͻ 0.05), whereas it remained unchanged for mutant C491A. Login to comment
165 Analysis of epithelia stably expressing these mutant CFTR proteins showed that, whereas C1344A-CFTR behaved as WT-CFTR, exhibiting reduced affinity for genistein at pH 8, the C491A mutation kept the same affinity for genistein at the three pHi values (Fig. 3C and Table 2). Login to comment
174 Substitution of either Cys-491 or Cys-1344 with alanine resulted in an increased affinity for the inhibitory site at pHi 6 and 7.35 (Table 2). Login to comment
175 This effect was more marked at pH 6 and for C1344A-CFTR (Ki ϭ 24 ␮M). Login to comment

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

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