ABCC7 p.His954Ala

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PMID: 20952391 [PubMed] Wang G et al: "State-dependent regulation of cystic fibrosis transmembrane conductance regulator (CFTR) gating by a high affinity Fe3+ bridge between the regulatory domain and cytoplasmic loop 3."
No. Sentence Comment
142 Consistent with involvement of CL3, another neighboring mutant H954A from CL3 was also amelioratory to Fe3ϩ (Fig. 4E), and its activity was increased by curcumin dramatically (data not shown).
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ABCC7 p.His954Ala 20952391:142:63
status: NEW
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145 In support of this proposal, H950A/H954A and D836A/C832A/ H774A completely prevented Fe3ϩ inhibition, which was reversed by EDTA (Fig. 4E).
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ABCC7 p.His954Ala 20952391:145:35
status: NEW
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PMID: 21059651 [PubMed] Wang G et al: "The inhibition mechanism of non-phosphorylated Ser768 in the regulatory domain of cystic fibrosis transmembrane conductance regulator."
No. Sentence Comment
143 In contrast, curcumin had no such effect on S737A and H954A mutants, suggesting that they may be weak inhibitory residues, although disulfide cross-linking of S737C to H954C strongly inhibited channel activity (Figs. 2E and 4E).
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ABCC7 p.His954Ala 21059651:143:54
status: NEW
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144 Because curcumin increased initial channel activity of most mutants at the R-CL3 interface after ATP was present, it is reasonable that subsequent PKA dependence was greatly reduced except for S737A and H954A.
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ABCC7 p.His954Ala 21059651:144:203
status: NEW
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234 Error bars, S.E. TABLE 1 Potential roles in hydrogen bonding at the CL3-R domain interface Note that mutants whose channel activity was increased by curcumin in the presence of ATP are highlighted in boldface type. Residues Role in H-bond Mutants Arg Strong donor H950R, S768R, H950R/S768R, H950R/S768D, H950D/S768R Asp Strong acceptor H950D, S768D, H950D/S768D, H950R/S768D, H950D/S768R Thr, Gln, Ser, His Donor/Acceptor H950Q, S768T, WT Ala Negative control K946A, H950A, K951A, H954A, S955A, Q958A, S737A, S768A, ⌬R Inhibition of CFTR by Ser768 JANUARY 21, 2011•VOLUME 286•NUMBER 3 JOURNAL OF BIOLOGICAL CHEMISTRY 2177 matter whether cAMP was present or not in the extracellular perfusate.
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ABCC7 p.His954Ala 21059651:234:481
status: NEW
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313 Similarly, His954 could not form an inhibitory H-bond with Ser768 because H954A was not dramatically activated by a combination of ATP and curcumin (Fig. 4E).
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ABCC7 p.His954Ala 21059651:313:74
status: NEW
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