ABCMdb

ABCC7 p.Ser492Pro

None has been submitted yet.

Publications

PMID: 22406676 [PubMed] Aleksandrov AA et al: "Allosteric modulation balances thermodynamic stability and restores function of DeltaF508 CFTR."

No. Sentence Comment

128 (c) Western blot of WT and ΔF508 CFTR expressed in HEK-293 cells and ΔF508 modified with I539T (ΔF/T), S422P/S434P/S492P/A534P (ΔF/4P), I539T/S492P (ΔF/PT), I539T/S492P/A534P (ΔF/2PT), and I539T/S422P/S434P/S492P/A534P (ΔF/4PT). Login to comment
136 Thermostable binding of the nucleotide by the WT, which is lost in ΔF508 CFTR,19 was not restored after rescue in cells grown at 27 °C [(r)ΔF panel], but was to some extent by I539T (ΔF/T panel), to a greater extent when S492P was added (ΔF/PT panel), still further with A534P also added (ΔF/2PT panel), and to near the WT level with proline replacements at residues S492 and A534 as well (ΔF/4PT panel). Login to comment
140 The addition of the S492P substitution generated a dominant full-conductance behavior (ΔF/PT), with a Po approximately half of the WT human channel at that temperature. Login to comment
143 Addition of S492P to form ΔF/PT resulted in WT-like full-conductance gating at temperatures up to approximately 37 °C, above which there was a transition to the ffm (middle tracing). Login to comment
144 Thus, as observed in the 35 °C fixed temperature recording (Fig. 6a), introduction of the Q-loop proline (S492P) had a significant stabilizing effect. Login to comment
178 HEK293 cells were transiently transfected with Cys-less CFTR or Cys-less ΔF508-CFTR in the presence or absence of the 4PT mutations (S422P/S434P/S492P/A534P/I539T), with the Cys pair V510C/G1069C introduced at the CL4/NBD1 interface. Login to comment
216 Introduction of a proline at S492 in the context of I539T increases the folding transition temperature of ΔF508 NBD1 to ~327 K, consistent with the observed decrease in thermal fluctuations upon S492P substitution (Fig. 9b, orange broken line). Login to comment
230 The apparent additive effects of several substituted prolines acting independently have been observed in other proteins as well.47 Molecular dynamics simulations reveal that the SDR of NBD1 is stabilized by the S492P substitution, and the stability further increases with each proline substitution. Login to comment

PMID: 23104983 [PubMed] He L et al: "Correctors of DeltaF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein."

No. Sentence Comment

85 Therefore, it serves as a basis for the comparison of the influence of the VX-809 compound with that of a known stabilizing second-site mutation, S492P (24). Login to comment
88 This behavior strongly contrasted that of the èc;F508/I539T variant with the stabilizing S492P mutation added, where transport capacity increased, and full conductance state persisted up to 35&#b0;C (compare tracings in Fig. 2Biii, iv). Login to comment
98 B) Single-channel recordings of èc;F508/I539T CFTR (èc;F/T) rescued by 3 òe;M VX-809 at 35&#b0;C (i) and 25&#b0;C (ii) and of èc;F508/I539T/S492P CFTR (èc;F/PT) as an example of an already known (24) alternative type of èc;F508/I539T, thermally stabilized by proline substitutions at 35&#b0;C (iii) and 25&#b0;C (iv). Login to comment
101 Two sets of 4 independent experiments of 35 and 38 min total time were used to estimate transport capacity ᐹॹᐺ afd; 0.85 afe; 0.26 at 25&#b0;C (iii) and ᐹॹᐺ afd; 3.14 afe; 0.32 at 35&#b0;C (iv) for èc;F508/I539T/S492P CFTR. Login to comment
122 4PT, S422P/S434P/S492P/ A534P/I539T. Login to comment
148 A) èc;F508 with NBD1-stabilizing mutations: 4S, I539T/G550E/R553M/R555K; èc;RI, deletion of amino acid residues 404-435; 4PT, S422P/S434P/S492P/A534P/I539T. Login to comment

PMID: 25083918 [PubMed] He L et al: "Restoration of NBD1 thermal stability is necessary and sufficient to correct F508 CFTR folding and assembly."

No. Sentence Comment

45 2PT, S492P/A534P/I539T; 4PT, 2PT + S422P/S434P; 3SS, G550E/R553M/R555K; 4SS, 3SS + I539T; ƊRI, deletion of RI amino acids 404-435; combo, ƊRI + 2PT + 3SS. Login to comment
65 1-WT; 2-S492P; 3-I539T; 4. Login to comment
66 S492P/I539T; 5-G550E/R553Q/R555K; 6-combo. Login to comment
72 2PT, S492P/ A534P/I539T; 3PT, 2PT + S495P. Login to comment
93 In addition to the S492P substitution found in three non-mammalian species that are relatively insensitive to the destabilizing influence of the ƊF508 mutation [13], we also included a second Q-loop proline substitution, S495P present in shark CFTR. Login to comment
95 S492P or I539T alone slightly increased the Tm of NBD1 (ƊTm = 2-3 &#b0;C) similar to the affect of the solubilization mutations F494N and Q637R combined. Login to comment
96 The S492P and I539T substitutions had additive affects such that ƊTm increased to 4.4 &#b0;C, and ƊTm was further increased to 8.4 &#b0;C when the additional mutations A534P/G550E/R553M/R555K were introduced. Login to comment
100 The effect of this single mutation was in contrast to that of S492P, which only increased maturation substantially when present together with I539T. Login to comment
123 Figure 3e shows that both BIA and BEIA further strongly increased maturation of the NBD1 stabilized variant ƊF508/2PT (S492P/A534P/I539T). Login to comment

PMID: 26149808 [PubMed] Chong PA et al: "Deletion of Phenylalanine 508 in the First Nucleotide-binding Domain of the Cystic Fibrosis Transmembrane Conductance Regulator Increases Conformational Exchange and Inhibits Dimerization."

No. Sentence Comment

386 Other published Q-loop segment suppressor mutations such as S492P and S495P (21, 29) are also likely to modulate NBD dimerization. Login to comment

PMID: 26384709 [PubMed] Aleksandrov LA et al: "Thermal stability of purified and reconstituted CFTR in a locked open channel conformation."

No. Sentence Comment

20 Abbreviations used: CFTR, cystic fibrosis transmembrane conductance regulator; ABC, ATP-binding cassette; NBD1, N-terminal nucleotide-binding domain; CF, cystic fibrosis; CHO, Chinese hamster ovary; HEK, human embryonic kidney; BHK, baby hamster kidney; Tm, melting temperature; Ti, inactivation temperature; RI, Regulatory Insertion (residues 404-435); 2PT, variant with NBD1 mutations S492P, A534P and I539T; Q loop, residues contacting the gamma-phosphate of ATP; SDR, structurally divers region; DMNG, Decyl Maltose Neopentyl Glycol; MALS, multi-angle light scattering analysis; DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanola mine; DOPC, 1,2-dioleoyl-sn-glycero-3-phosphocholine; DOPS, 1,2-dioleoyl-sn- glycero-3-phospho-L-serine; SUV, small unilamellar vesicles; LMV, large multilamellar vesicles; LULV, large unilamellar vesicles; PKA, protein kinase A; RIPA, radioimmunoprecipitation assay; ER, endoplasmic reticulum; RAMP, gradual increase with constant slope. Login to comment
107 As seen in Fig. 2a the ''2PT" variant with NBD1 mutations S492P, A534P and I539T and the DRI variant, from which the Regulatory Insertion (residues 404-435) was deleted both increased expression levels substantially compared to the wild type. Login to comment
109 Channel open probability was substantially reduced in 2PT due to the introduction of the two prolines into the mobile Q loop (S492P) and SDR (A534P) regions of NBD1 (third tracing). Login to comment

PMID: 26517912 [PubMed] Bose SJ et al: "Exploiting species differences to understand the CFTR Cl- channel."

No. Sentence Comment

120 Hypothesizing that structural differences between human and chicken CFTR account for the thermostability of F508del chicken CFTR, Aleksandrov et al. [41] demonstrated that the F508del revertant I539T and four proline residues at key positions within NBD1 (S422P, S434P, S492P and A534P) were responsible for rescuing the processing, plasma membrane stability and function of human CFTR. Login to comment