ABCMdb

ABCC7 p.Lys464Gln

None has been submitted yet.

Publications

PMID: 8741733 [PubMed] Wilkinson DJ et al: "CFTR: the nucleotide binding folds regulate the accessibility and stability of the activated state."

No. Sentence Comment

19 In contrast, mutations in the putative ATP-binding pockets of the two NBFs produced opposite results, a reduction in sensitivity for mutations in NBF1 (K464Q, D572N) and an increase in sensitivity for the analogous mutations in NBF2 (K12500~ D1370N). Login to comment
60 Representative time courses are shown for wild type CFTR and two variants, K464Q and K1250Q. Login to comment
65 In contrast, the decline in gel for mutants such as K464Q was rapid, showing only a slight increase after IBMX withdrawal. Login to comment
75 In previous studies (Drumm et al., 1991; Snfit et al., 1993), we estimated the apparent KAfor dose-dependent activation from loga- WILKINSON ET AL. A B A 100 v 80 o 4O 2O - 0 A K464Q ~ - ~ 9 wild type I , , , ,i , ,, , i , ,, , i , , , ,l ,, , , i , , , , 0 10 20 30 40 50 60 minutes .37 O .14 I I 0 10 2o I I I I I I I I I i lO 20 minutes 60 120 FmURE 2. Login to comment
76 (A) Representative time courses for deactivation of wild type CFTR (0) and the analogous lysine to glutamine mutants in NBF1 (K464Q, A) and NBF2 (K1250Q, ~). Login to comment
79 In the experiments shown, the values of gel(max) for wild-type CFTR, K464Q, and K1250Q were 27.9, 36.3, and 30.3 I,S, and the corresponding minimum membrane conductances alter deactivation of CFTR were 2.1, 0.7, and 1.0 ~S, respectively. Login to comment
82 For wild-type (0), K464Q (A), and KI250Q (~), the values of *k,,a determined from linear regressions (lines) were 0.134, 0.166, and 0.019 rain -l, and the corresponding regression coefficients (r e) were 0.957, 0.999, and 0.998, respectively. Login to comment
83 rithmic dose-response plots, but for comparison with rates of activation we sought a more unbiased estimate of Ka that took into account three factors: (1) the activation produced by forskolin alone, (2) the block of CFTR by high concentrations of IBMX, and (3) the fact that for insensitive mutants such as G551D, D572N, and G1349D the dose-response showed no tendency toward saturation at the highest concentrations of IBMX. Login to comment
99 For wild-wpe CFTR and the mutant K464Q, the observed values of ~'!i'• were ~60% and 27% of the theoretical maximum g'cl, respectively. Login to comment
129 (B) IBMX dose-response relations for steady state activation of K1250A (~), wild-type CFTR (Q, n = 26), and K464Q (A, n = 5). Login to comment
133 In Fig. 3 B, the activation components for wild-type CFTR and the mutants K1250A and K464Q were simulated by adding back the blocked component and plotting the adjusted data points along with the curves calculated using the estimated KAvalues. Login to comment
195 a~ODiap- 9 K464Q a I ' ' ' ' I ' ' ' ' I ' ' 0 10 20 ~ O -0 0, 9 -0~176176176o ....... 9.... -o*- -o*- 9 i~ e'~176176176176 9 D572N o i , , , , i , , , , i , , , , I , , , , i , , , , i , , , , 0 I0 20 30 40 50 minutes K1250A K1250C I i 30 D1370N 6O FIGURE4. Login to comment
229 The calculated values of k,,~.for K464Q and K464A indicated that the substitutions to alanine or glutamine also increased the off rate under activating conditions, which contributed to the increase in Ka and compensated somewhat for the reduction in relaxation rate caused by the reduced on rate. Login to comment
237 O *o ~ q. v~ ,,~,,s =~ ..... ===o~ _ -~-...-0 ------=._.a ~..~..-9:...e..o.~ * ............. "" "o~'"(~ -~ 9o O ~ - -oO- - - - ,u -- * ~- - - Z~, I ' ' ' ' [ .... ' I ' ' ' ' I ' ' ' ' I ' ' ' ' 0 10 20 30 40 50 \ "0,'~-.= " K464Q o K1250( " " ::'~:.-. Login to comment
281 + kott) (10-3 min-l kon kofr latency *k~m CFTR (mM) n (10-3min-]) mM-1) (10-3min 1) (10-3min-l) n (min) (10 3min i) n wt 0.65 • 0.08 26 664 • 51 118 • 9 558 • 45 76-+ 6 20 6.0 • 0.3 88 • 6 16 K464R 2.6 • 0.1": 4 153 + 20**+ 20 • 3*** 101 • 13''` 52 • 7*: 5 1.3 • 0.2*++ 174 • 14"** 7 K464Q 3.3 • 0.5"* 5 331 • 56*** 40 -+ 7* 199 • 34* 132 • 22*'` 5 1.9 • 0.3"I 142 -+ 19''` 5 K464A 4.6 • 0.7** 6 289 • 49* 30 • 5** 151 • 26*** 139 • 24*: 7 1.1 • 0.1"** 133 • 14"** 8 D572N 9.3 + 0.02*: 6 106 • 7*: 7-+0.5*: 37-+3*** 69 • 5+* 4 0.9 • 0.2*** 245 • 32*: 3 K1250R 0.17 • 0.07*: 5 239 •33*** 46 -+ 6"+* 231 • 32*: 8 • 1": 10 10.4 • 0.8"~ 100 • 7** 6 K1250Q 0.12 • 0.04*** 5 150 • 18''` 29 • 4* 146 -+ 18" 4 + 0.4"I 5 22.3 • 2.4*: 30 •5": 5 K1250A 0.07 + 0.02*: 10 218 • 18" 43 • 4*'` 215 • 18": 3 -+0.3*~* 5 15.6-+ 1.0"** 43 -+5** 5 D1370N 0.16 + 0.04*'` 7 449 - 79*: 87 • 15: 435 +76** 14 - 2*: 5 16.3-4-1.2"" 69-+ 6** 5 The symbols (*) and ('`) indicate significant differences from wild-type CFTR and the analogous mutant, respectively (P < 0.05). Login to comment
61 Representative time courses are shown for wild type CFTR and two variants, K464Q and K1250Q. Login to comment
66 In contrast, the decline in gel for mutants such as K464Q was rapid, showing only a slight increase after IBMX withdrawal. Login to comment
77 (A) Representative time courses for deactivation of wild type CFTR (0) and the analogous lysine to glutamine mutants in NBF1 (K464Q, A) and NBF2 (K1250Q, ~). Login to comment
80 In the experiments shown, the values of gel(max) for wild-type CFTR, K464Q, and K1250Q were 27.9, 36.3, and 30.3 I,S, and the corresponding minimum membrane conductances alter deactivation of CFTR were 2.1, 0.7, and 1.0 ~S, respectively. Login to comment
100 For wild-wpe CFTR and the mutant K464Q, the observed values of ~'!i'ߦ were ~60% and 27% of the theoretical maximum g'cl, respectively. Login to comment
131 (B) IBMX dose-response relations for steady state activation of K1250A (~), wild-type CFTR (Q, n = 26), and K464Q (A, n = 5). Login to comment
135 In Fig. 3 B, the activation components for wild-type CFTR and the mutants K1250A and K464Q were simulated by adding back the blocked component and plotting the adjusted data points along with the curves calculated using the estimated KAvalues. Login to comment
198 a~ODiap- 9 K464Q a I ' ' ' ' I ' ' ' ' I ' ' 0 10 20 ~ O -0 0, 9 -0 ~176176176 o ....... 9.... -o*- -o*- 9 i~ e'~176176176176 9 D572N o i , , , , i , , , , i , , , , I , , , , i , , , , i , , , , 0 I0 20 30 40 50 minutes K1250A K1250C I i 30 D1370N 6O FIGURE4. Login to comment
231 The calculated values of k,,~.for K464Q and K464A indicated that the substitutions to alanine or glutamine also increased the off rate under activating conditions, which contributed to the increase in Ka and compensated somewhat for the reduction in relaxation rate caused by the reduced on rate. Login to comment
239 O *o ~ q. v~ ,,~,,s =~ ..... ===o~ _ -~-... -0 ------=._.a ~..~..-9:...e..o.~ * ..... ........ "" "o~'"(~ -~ 9o O ~ - -oO- - - - ,u -- * ~- - - Z~, I ' ' ' ' [ .... ' I ' ' ' ' I ' ' ' ' I ' ' ' ' 0 10 20 30 40 50 \ "0,'~-.= " K464Q o K1250( " " ::'~:.-. Login to comment
283 + kott) (10-3 min-l kon kofr latency *k~m CFTR (mM) n (10-3 min-]) mM-1) (10-3 min 1) (10-3min-l) n (min) (10 3min i) n wt 0.65 ߦ 0.08 26 664 ߦ 51 118 ߦ 9 558 ߦ 45 76 -+ 6 20 6.0 ߦ 0.3 88 ߦ 6 16 K464R 2.6 ߦ 0.1": 4 153 + 20**+ 20 ߦ 3*** 101 ߦ 13''` 52 ߦ 7*: 5 1.3 ߦ 0.2*++ 174 ߦ 14"** 7 K464Q 3.3 ߦ 0.5"* 5 331 ߦ 56*** 40 -+ 7* 199 ߦ 34* 132 ߦ 22*'` 5 1.9 ߦ 0.3"I 142 -+ 19''` 5 K464A 4.6 ߦ 0.7** 6 289 ߦ 49* 30 ߦ 5** 151 ߦ 26*** 139 ߦ 24*: 7 1.1 ߦ 0.1"** 133 ߦ 14"** 8 D572N 9.3 + 0.02*: 6 106 ߦ 7*: 7 -+0.5*: 37 -+3*** 69 ߦ 5+* 4 0.9 ߦ 0.2*** 245 ߦ 32*: 3 K1250R 0.17 ߦ 0.07*: 5 239 ߦ 33*** 46 -+ 6"+* 231 ߦ 32*: 8 ߦ 1": 10 10.4 ߦ 0.8"~ 100 ߦ 7** 6 K1250Q 0.12 ߦ 0.04*** 5 150 ߦ 18''` 29 ߦ 4* 146 -+ 18" 4 + 0.4"I 5 22.3 ߦ 2.4*: 30 ߦ 5": 5 K1250A 0.07 + 0.02*: 10 218 ߦ 18" 43 ߦ 4*'` 215 ߦ 18": 3 -+0.3*~* 5 15.6 -+ 1.0"** 43 -+5** 5 D1370N 0.16 + 0.04*'` 7 449 - 79*: 87 ߦ 15: 435 + 76** 14 - 2*: 5 16.3 -4-1.2"" 69 -+ 6** 5 The symbols (*) and ('`) indicate significant differences from wild-type CFTR and the analogous mutant, respectively (P < 0.05). Login to comment

PMID: 7540563 [PubMed] Manavalan P et al: "Sequence homologies between nucleotide binding regions of CFTR and G-proteins suggest structural and functional similarities."

No. Sentence Comment

171 The NBDI mutations (K464Q, D572N) showed a decrease in sensitivity to IBMX activation while the equivalent NBD2 mutations (KI250Q, DI370N) produced an increase in IBMX sensitivity, These results together with our sequence analysis data suggest that the nature of nuclcotide binding and the subsequent conforma- tior~:,lchanges may differ for the two domains. Login to comment
170 The NBDI mutations (K464Q, D572N) showed a decrease in sensitivity to IBMX activation while the equivalent NBD2 mutations (KI250Q, DI370N) produced an increase in IBMX sensitivity, These results together with our sequence analysis data suggest that the nature of nuclcotide binding and the subsequent conforma- tior~:,lchanges may differ for the two domains. Login to comment

PMID: 7694298 [PubMed] Smit LS et al: "Functional roles of the nucleotide-binding folds in the activation of the cystic fibrosis transmembrane conductance regulator."

No. Sentence Comment

92 The dose- 100- g 80-E C3) ° 60- V ai) X 40- E co 20 NBF1 O O G551S (9) v-v G551D (6) 0 Owt (12) T 6o NBF1 + NBF2 O--O G551S + G1349S (7) *--* G551 D + G 1 349D (5) Oz0 6 0 / T/ * , * /1 ° T 0 r / / / 3 _ -- ........ 0.02 0.05 0.2 0.5 1 2 IBMX, mM O-O wt (12) V-V K464Q ( 4) 1OOT 9 80E 0I-) I00160- -0 . Login to comment