ABCC7 p.Thr338His

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PMID: 14598388 [PubMed] Liu X et al: "CFTR: what's it like inside the pore?"
No. Sentence Comment
117 Titration of the macroscopic conductance due to T338C and T338H CFTR indicates that positive charges at R334, perhaps at K335, and perhaps elsewhere may cause the pKa of T338C CFTR to become more acidic than in free solution (E7.4) and to render T338H CFTR non-titratable.
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ABCC7 p.Thr338His 14598388:117:58
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ABCC7 p.Thr338His 14598388:117:246
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118 Changing the charge at position 334 either by modification of R334C/T338H CFTR with polar thiol reactive reagents or by amino acid substitution (R334A/T338C) shifts the titration curve in a direction that was predicted on the basis of a nearby positive charge being able to stabilize a titratable group (Liu et al., 2001).
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ABCC7 p.Thr338His 14598388:118:68
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PMID: 16436375 [PubMed] Liu X et al: "Variable reactivity of an engineered cysteine at position 338 in cystic fibrosis transmembrane conductance regulator reflects different chemical states of the thiol."
No. Sentence Comment
53 RESULTS T338C/WT CFTR Conductance Was Markedly Altered by 2-ME or DTT Prior to Exposure to Exogenous Thiol-directed Reagents5 - Exposing oocytes expressing T338C/WT CFTR to 2-ME or DTT during steady state activation led to increases in conductance (without any discernable change in reversal potential) that were rapid (t1/2 ϭ 20 s), and of variable amplitude and were not seen in oocytes expressing CFTR constructs lacking the cysteine at 338, such as WT, T338A, T338H, T338S CFTR, or Cys-less CFTR.
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ABCC7 p.Thr338His 16436375:53:470
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PMID: 15361410 [PubMed] Liu X et al: "CFTR: a cysteine at position 338 in TM6 senses a positive electrostatic potential in the pore."
No. Sentence Comment
94 For ease of comparison, in T338C/R334X (X ¼ A or E) CFTRs and T338H/R334C CFTRs in which the cysteine was always blocked by reaction with MTS reagents or NEM, the titration curves were expressed in a normalized form.
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ABCC7 p.Thr338His 15361410:94:66
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190 To test the generality of titration results obtained with T338C CFTR, we compared the titration behavior of T338H CFTR with that of a double mutant, T338H/R334C, in which it was possible to change the charge at position 334 by means of chemical modification.
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ABCC7 p.Thr338His 15361410:190:108
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ABCC7 p.Thr338His 15361410:190:149
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191 Summarized in Fig. 8 B are the results obtained from oocytes expressing either T338H or chemically modified T338H/R334C CFTR (n ¼ 3-4 for each mutant).
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ABCC7 p.Thr338His 15361410:191:79
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ABCC7 p.Thr338His 15361410:191:108
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ABCC7 p.Thr338His 15361410:191:149
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192 Shown are sample titration curves for T338H and T338H/R334C CFTRs in which the cysteine was modified by MTSET1 , MTSESÿ , and NEM (neutral).
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ABCC7 p.Thr338His 15361410:192:38
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ABCC7 p.Thr338His 15361410:192:48
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ABCC7 p.Thr338His 15361410:192:79
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ABCC7 p.Thr338His 15361410:192:108
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194 The conductance of oocytes expressing T338H CFTR was essentially not titratable, as if the pKa of the histidine was more acidic than 4.0.
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ABCC7 p.Thr338His 15361410:194:38
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195 Similarly, the conductance due to MTSET1 -modified T338H/R334C CFTR was not very sensitive to pH titration.
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ABCC7 p.Thr338His 15361410:195:38
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ABCC7 p.Thr338His 15361410:195:51
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208 NEM- or MTSESÿ -modified T338H/R334C CFTR were more titratable and the apparent pKa values were shifted toward more basic values.
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ABCC7 p.Thr338His 15361410:208:30
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209 Because the range of pH values tolerated by oocytes was limited, the apparent pKa values could not be estimated accurately for T338H and T338H/ R334C variants.
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ABCC7 p.Thr338His 15361410:209:25
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ABCC7 p.Thr338His 15361410:209:127
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ABCC7 p.Thr338His 15361410:209:137
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221 FIGURE 8 The pH-induced changes in the conductances of oocytes expressing T338C/R334A, T338C/R334E, T338H, or T338H/R334C CFTR.
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ABCC7 p.Thr338His 15361410:221:100
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ABCC7 p.Thr338His 15361410:221:110
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222 (A) Sample titration curves of conductances of oocytes expressing T338C CFTR (solid circles), T338C/R334A (open squares), or T338C/ R334E CFTRs (shaded triangles).
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ABCC7 p.Thr338His 15361410:222:100
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ABCC7 p.Thr338His 15361410:222:110
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225 (B) Sample titration curves for T338H (open triangle) and T338H/R334C CFTR modified by MTSET1 (solid circles), MTSESÿ (open circles), and NEM (shaded triangles).
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ABCC7 p.Thr338His 15361410:225:32
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ABCC7 p.Thr338His 15361410:225:58
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193 Shown are sample titration curves for T338H and T338H/R334C CFTRs in which the cysteine was modified by MTSET1 , MTSES , and NEM (neutral).
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ABCC7 p.Thr338His 15361410:193:38
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ABCC7 p.Thr338His 15361410:193:48
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196 Similarly, the conductance due to MTSET1 -modified T338H/R334C CFTR was not very sensitive to pH titration.
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ABCC7 p.Thr338His 15361410:196:51
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210 Because the range of pH values tolerated by oocytes was limited, the apparent pKa values could not be estimated accurately for T338H and T338H/ R334C variants.
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ABCC7 p.Thr338His 15361410:210:127
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ABCC7 p.Thr338His 15361410:210:137
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226 (B) Sample titration curves for T338H (open triangle) and T338H/R334C CFTR modified by MTSET1 (solid circles), MTSES (open circles), and NEM (shaded triangles).
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ABCC7 p.Thr338His 15361410:226:32
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ABCC7 p.Thr338His 15361410:226:58
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