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Literature summary extracted from

  • Lin, W.Y.; Jih, K.Y.; Hwang, T.C.
    A single amino acid substitution in CFTR converts ATP to an inhibitory ligand (2014), J. Gen. Physiol., 144, 311-320.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
5.6.1.6 recombinant expression of wild-type and mutant enzymes in CHO cells Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
5.6.1.6 G551D third most common pathogenic naturally occuring mutation of the enzyme, mutant G551D shows a significantly decreased open probability caused by failure of the mutant channel to respond to ATP. The CFTR-targeted drug, VX-770 (Ivacaftor) potentiates G551D-CFTR function in vitro by boosting its open probability, in the presence of VX-770, G551D-CFTR becomes responsive to ATP, albeit with an unusual time course. A sudden removal of ATP in excised inside-out patches containing the mutant enzyme elicits an initial increase in macroscopic G551D-CFTR current followed by a slow decrease, in contrast to wild-type channels. The stimulatory effect of ATP is abolished by the G551D mutation despite a normal surface expression of the mutant proteins. The two ATP-binding sites in the G551D mutant mediate opposite effects on channel gating. Introduction of mutations that specifically alter ATP-binding affinity in either nucleotide-binding domain (NBD1 or NBD2) into the G551D background, the disease-associated mutation converts site 2, formed by the head subdomain of NBD2 and the tail subdomain of NBD1, into an inhibitory site, whereas site 1 remains stimulatory Homo sapiens
5.6.1.6 G551D/Y1219F increased ATP washout compared to mutant G551D Homo sapiens
5.6.1.6 G551D/Y1219G increased ATP washout compared to mutant G551D Homo sapiens
5.6.1.6 G551D/Y1219I increased ATP washout compared to mutant G551D Homo sapiens
5.6.1.6 G551E site-directed mutagenesis, the mutant exhibits a similar phenotype like mutant G551D Homo sapiens
5.6.1.6 G551K site-directed mutagenesis, the mutant does not exhibit a similar phenotype like mutant G551D Homo sapiens
5.6.1.6 G551S site-directed mutagenesis, the mutant does not exhibit a similar phenotype like mutant G551D Homo sapiens
5.6.1.6 W401G/G551D acceleration of the slow-phase current decay by the W401G mutation Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
5.6.1.6 cell surface
-
 Homo sapiens 9986
-
5.6.1.6 plasma membrane
-
 Homo sapiens 5886
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
5.6.1.6 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
5.6.1.6 ATP + H2O + closed Cl- channel Homo sapiens
-
 ADP + phosphate + open Cl- channel
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
5.6.1.6 Homo sapiens P13569
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5.6.1.6 ATP + H2O + closed Cl- channel
-
 Homo sapiens ADP + phosphate + open Cl- channel
-
 ?

Synonyms

EC Number Synonyms Comment Organism
5.6.1.6 CFTR
-
 Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
5.6.1.6 7.4
-
 assay at Homo sapiens

General Information

EC Number General Information Comment Organism
5.6.1.6 malfunction cystic fibrosis, one of the most common lethal genetic diseases, is caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a chloride channel. The third most common pathogenic mutation, a glycine-to-aspartate mutation at position 551 (G551D) shows a significantly decreased open probability caused by failure of the mutant channel to respond to ATP. The CFTR-targeted drug, VX-770 (Ivacaftor), which potentiates G551D-CFTR function in vitro by boosting its Po, is approved by the american food and drug administration to treat cystic fibrosis patients carrying this mutation Homo sapiens
5.6.1.6 physiological function the cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a chloride channel, which is gated by ATP when phosphorylated Homo sapiens