ABCMdb

ABCC7 p.Tyr1219Trp

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Publications

PMID: 16966475 [PubMed] Zhou Z et al: "The two ATP binding sites of cystic fibrosis transmembrane conductance regulator (CFTR) play distinct roles in gating kinetics and energetics."

No. Sentence Comment

105 A more conserved mutation (Y1219W) does not change the K1/2 value significantly. Login to comment
122 (A) Normalized ATP dose-response relationships of WT (black line, Michaelis-Menten fit from Fig. 1 D), Y1219W (brown), Y1219F (pink), Y1219I (blue), and Y1219G (green line, Michaelis-Menten fit from Fig. 1 D). Login to comment
124 K1/2 values are 0.13 ± 0.02 mM (Y1219W), 0.46 ± 0.06 mM (Y1219F), and 0.94 ± 0.20 mM (Y1219I), respectively. Login to comment

PMID: 18391167 [PubMed] Chen TY et al: "CLC-0 and CFTR: chloride channels evolved from transporters."

No. Sentence Comment

786 A more conservative mutation (Y1219W), however, did not change the K0.5 value significantly. Login to comment

PMID: 20628841 [PubMed] Shimizu H et al: "A stable ATP binding to the nucleotide binding domain is important for reliable gating cycle in an ABC transporter CFTR."

No. Sentence Comment

19 The degree of dose-response shift, a descending order of Y1218G, Y1219I, Y1219F and Y1219W, seemed to depend on the similarity of chemical properties, e.g., hydrophobicity and p bond by aromatic ring, of the side chains introduced by the mutations to tyrosine. Login to comment
59 Figure 2b compares macroscopic current relaxations for Y1219G, Y1219I, Y1219F and Y1219W mutants. Login to comment
60 Although a slow phase of current decay can be seen with Y1219G and Y1219I, this second phase is hardly discernable for the Y1219W mutant. Login to comment
65 b A representative current trace of WT-CFTR channel showing immediate closing upon a rapid removal of ATP somewhere between Y1219W and Y1219I. Login to comment
67 The time constants of the initial fast phase for all the Y1219 mutants are within hundreds of milliseconds (sfast: 504 &#b1; 76 ms, n = 5 for Y1219G; 450 &#b1; 44 ms, n = 7 for Y1219I; 571 &#b1; 142 ms, n = 4 for Y1219F; 513 &#b1; 66 ms, n = 5 for Y1219W) and there is not significant difference in the fast time constant among these Y1219 mutants (Fig. 2b). Login to comment
68 On the other hand, the time constants of the slow component for Y1219F and Y1219W are shorter than those of Y1219G and Y1219I (Fig. 3a). Login to comment
69 More importantly, the fraction of the slow component (Fig. 3b) shows a gradual decrease as the mutation becomes less 'preserved` (Y1219G [ Y1219I [ Y1219F [ Y1219W). Login to comment
70 It should be noted that, for technical reasons (detailed in ''Discussion``), our calculation of the fraction of the slow component is somewhat overestimated for Y1219F and Y1219W. Login to comment
71 The actual values for Y1219F and Y1219W are lower than those shown in Fig. 3b. Login to comment
80 b Macroscopic current relaxations upon ATP wash-out for Y1219G, Y1219I, Y1219F and Y1219W. Login to comment
82 The time constant and the fraction of the slow component are summarized in Fig. 3. c Single channel recording of Y1219G-CFTR showing a long opening even after ATP removal 35 30 25 20 15 10 5 0 Y1219G Y1219I Y1219F Y1219W 0.5 0.4 0.3 0.2 0.1 0.0 Y1219G Y1219I Y1219F Y1219W A slow / (A slow + A fast ) c4; slow (s) A B Fig. 3 Kinetic parameters of macroscopic current relaxations for Y1219G, Y1219I, Y1219F and Y1219W. Login to comment
83 a Time constants of the slow component of the current relaxation for the Y1219 mutants. Y1219G: n = 5; Y1219I: n = 7; Y1219F: n = 4; and Y1219W: n = 5. b Fraction of the slow component (Aslow/Aslow ? Login to comment
84 Afast) for the Y1219 mutants. Y1219G: n = 5; Y1219I: n = 7; Y1219F: n = 4; and Y1219W: n = 5 ATP because of their similar rate-limiting hydrolyzing rates [11]. Login to comment
132 Although the results with Y1219G and Y1219I mutations are quantified accurately, this may not be the case with the data for Y1219F and Y1219W. Login to comment
133 First, like WT-CFTR, the slow component for Y1219W is too obscure for reliable curve fitting. Login to comment
162 If different mutations at Y1219 can affect the entry rate and the exit rate differently as shown in Table 2, this hypothesis may explain most of the results Table 1 Parameter sets (s-1 ) for the ''kiss and run`` hypothesis kCO1 kO1C kO1O2 kO2C Y1219G 3 or 0a 3 2 9 10-2 3.8 9 10-2 Y1219I : : 1.3 9 10-2 : Y1219F : : 1.1 9 10-2 : Y1219W : : 4 9 10-3 : a kCO1 was set to 3 s-1 for simulating the ''with ATP`` condition and 0 s-1 for simulating the ''after the ATP washout`` condition. Login to comment
166 b Representative reproduced macroscopic current relaxations mimicking those in Y1219G (red), Y1219I (green), Y1219F (cyan) and Y1219W (blue). Login to comment