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Literature summary for 5.6.1.6 extracted from

  • Wellhauser, L.; Chiaw, P.K.; Pasyk, S.; Li, C.; Ramjeesingh, M.; Bear, C.E.
    A small-molecule modulator interacts directly with DELTAPhe508-CFTR to modify its ATPase activity and conformational stability (2009), Mol. Pharmacol., 75, 1430-1438.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
VRT-532 i.e. 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)-phenol, the ATPase activity of the purified and reconstituted mutant DELTAPhe508-CFTR is directly modulated and ATP turnover is decreased by binding of VRT-532, but VRT-532 stimulates channel function of DELTAPhe508-CFTR in cells. VRT-532 binding induces a change in conformational stability of the C-terminal half of DELATPhe508-CFTR Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of mutant DELTAPhe508 in BHK cells and as His-tagged protein in Spodoptera frugiperda Sf9 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information deletion of Phe508 constitutes the most prevalent of a number of mutations in CFTR that cause cystic fibrosis, mutation leads to CFTR misfolding and retention in the endoplasmic reticulum, as well as impaired channel activity. The biosynthetic defect can be partially overcome by small molecule correctors, once at the cell surface, small-molecule potentiators enhance the channel activity of DELTAPhe508 CFTR, VRT-532 exhibit both corrector and potentiator functions Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
CFTRinh-172 a specific CFTR inhibitor, inhibits ATPase activity of mutant DELTAPhe508-CFTR Homo sapiens
VRT-532 i.e. 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)-phenol, the ATPase activity of the purified and reconstituted mutant DELTAPhe508-CFTR is directly modulated and ATP turnover is decreased by binding of VRT-532, but VRT-532 stimulates channel function of DELTAPhe508-CFTR in cells. VRT-532 binding induces a change in conformational stability of the C-terminal half of DELATPhe508-CFTR Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.2
-
ATP pH 7.5, 37°C, mutant DELTAPhe508-CFTR Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane
-
Homo sapiens 16020
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O + closed Cl- channel Homo sapiens the enzyme also shows ion channel activity ADP + phosphate + open Cl- channel
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein
-
Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged mutant DELTAPhe508 from Sf9 cells by nickel affinity chromatography Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O + closed Cl- channel
-
Homo sapiens ADP + phosphate + open Cl- channel
-
?
ATP + H2O + closed Cl- channel the enzyme also shows ion channel activity Homo sapiens ADP + phosphate + open Cl- channel
-
?

Subunits

Subunits Comment Organism
? x * 140000-150000, recombinant mutant DELTAPhe508, SDS-PAGE Homo sapiens

Synonyms

Synonyms Comment Organism
CFTR
-
Homo sapiens
cystic fibrosis transmembrane conductance regulator
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
27
-
ion channel assay at Homo sapiens
37
-
ATPase assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
ion channel assay at Homo sapiens
7.5
-
ATPase assay at Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0026
-
pH 7.5, 37°C, inhibition of ATPase activity of mutant DELTAPhe508-CFTR Homo sapiens CFTRinh-172