BRENDA - Enzyme Database

ATP and AMP mutually influence their interaction with the ATP-binding cassette (ABC) adenylate kinase cystic fibrosis transmembrane conductance regulator (CFTR) at separate binding sites

Randak, C.O.; Dong, Q.; Ver Heul, A.R.; Elcock, A.H.; Welsh, M.J.; J. Biol. Chem. 288, 27692-27701 (2013)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
2.7.4.3
wild-type and mutant CFTR are transiently expressed in HeLa cell membranes a double vaccinia virus/T7 RNA polymerase system
Homo sapiens
5.6.1.6
transient expression of either wild-type or mutant enzymes in HeLa cell membranes using a vaccinia virus/T7 RNA polymerase expression system
Homo sapiens
Engineering
EC Number
Amino acid exchange
Commentary
Organism
5.6.1.6
A462F
site-directed mutagenesis, the mutation abolishes nucleotide interaction with ATP-binding site 1, the mutant exhibits a low, ATP-dependent open probability due to a reduced opening rate with a normal burst duration. The A462F mutation interfers with processing and trafficking to the cell membrane
Homo sapiens
5.6.1.6
D1370N
site-directed mutagenesis of a conserved residue in the Walker B motif of ATP-binding site 2, the mutation abolishes P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
Homo sapiens
5.6.1.6
D572N
site-directed mutagenesis of a conserved residue in the Walker B motif of ATP-binding site 1, the mutation does not abolish P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
Homo sapiens
5.6.1.6
K1250A
site-directed mutagenesis of a conserved residue in the Walker A motif of ATP-binding site 2, the mutation abolishes P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
Homo sapiens
5.6.1.6
K464A
site-directed mutagenesis of a conserved residue in the Walker A motif of ATP-binding site 1, the mutation does not abolish P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
Homo sapiens
5.6.1.6
additional information
photolabeling of CFTR with 8-N3-[32P]AMP or 8-N3-[32P]ATP
Homo sapiens
5.6.1.6
S1248F
site-directed mutagenesis, the mutation abolishes nucleotide interaction with ATP-binding site 2, the mutant exhibits a low, ATP-dependent open probability due to a reduced opening rate with a normal burst duration. The S1248F mutation does not interfere with processing and trafficking to the cell membrane
Homo sapiens
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
2.7.4.3
P1,P4-di(adenosine-5') tetraphosphate
Ap4A
Homo sapiens
2.7.4.3
P1,P5-di(adenosine-5') pentaphosphate
Ap5A, interacts simultaneously with an AMP-binding site and ATP-binding site 2
Homo sapiens
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
5.6.1.6
membrane
-
Homo sapiens
16020
-
Metals/Ions
EC Number
Metals/Ions
Commentary
Organism
Structure
2.7.4.3
Mg2+
required
Homo sapiens
5.6.1.6
Mg2+
required
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2.7.4.3
ATP + AMP
Homo sapiens
-
2 ADP
-
-
r
2.7.4.3
additional information
Homo sapiens
the cystic fibrosis transmembrane conductance regulator (CFTR) has adenylate kinase activity as an ABC adenylate kinase. ATP enables CFTR photolabeling by 8-N3-AMP, and AMP increases 8-N3-ATP photolabeling at ATP-binding site 2. AMP interacts with CFTR in an ATP-dependent manner and alters ATP interaction with the adenylate kinase active center ATP-binding site. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, also have adenylate kinase activity. All three ABC adenylate kinases bind and hydrolyze ATP in the absence of other nucleotides
?
-
-
-
5.6.1.6
ATP + H2O + closed Cl- channel
Homo sapiens
-
ADP + phosphate + open Cl- channel
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
2.7.4.3
Homo sapiens
-
-
-
5.6.1.6
Homo sapiens
P13569
-
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.7.4.3
ATP + AMP
-
734231
Homo sapiens
2 ADP
-
-
-
r
2.7.4.3
additional information
the cystic fibrosis transmembrane conductance regulator (CFTR) has adenylate kinase activity as an ABC adenylate kinase. ATP enables CFTR photolabeling by 8-N3-AMP, and AMP increases 8-N3-ATP photolabeling at ATP-binding site 2. AMP interacts with CFTR in an ATP-dependent manner and alters ATP interaction with the adenylate kinase active center ATP-binding site. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, also have adenylate kinase activity. All three ABC adenylate kinases bind and hydrolyze ATP in the absence of other nucleotides
734231
Homo sapiens
?
-
-
-
-
5.6.1.6
ATP + H2O + closed Cl- channel
-
734231
Homo sapiens
ADP + phosphate + open Cl- channel
-
-
-
?
5.6.1.6
additional information
in the presence of ATP and physiologically relevant concentrations of AMP, the enzyme exhibits adenylate kinase activity, converting ATP and AMP into 2 ADP and vice versa. The interaction of nucleotide triphosphate with the enzyme at ATP-binding site 2 is required for this activity. ATP and AMP interact with separate binding sites but mutually influence their interaction with the ABC adenylate kinase CFTR, the active center of the adenylate kinase comprises ATP-binding site 2
734231
Homo sapiens
?
-
-
-
-
Subunits
EC Number
Subunits
Commentary
Organism
5.6.1.6
More
construction of a putative molecular three-dimensional model of the nucleotide-binding domain 1-nucleotide-binding domain 2 heterodimer
Homo sapiens
Temperature Optimum [°C]
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
5.6.1.6
23
26
assay at room temperature
Homo sapiens
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
2.7.4.3
7.5
-
assay at
Homo sapiens
5.6.1.6
7.3
-
assay at
Homo sapiens
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
2.7.4.3
wild-type and mutant CFTR are transiently expressed in HeLa cell membranes a double vaccinia virus/T7 RNA polymerase system
Homo sapiens
5.6.1.6
transient expression of either wild-type or mutant enzymes in HeLa cell membranes using a vaccinia virus/T7 RNA polymerase expression system
Homo sapiens
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
5.6.1.6
A462F
site-directed mutagenesis, the mutation abolishes nucleotide interaction with ATP-binding site 1, the mutant exhibits a low, ATP-dependent open probability due to a reduced opening rate with a normal burst duration. The A462F mutation interfers with processing and trafficking to the cell membrane
Homo sapiens
5.6.1.6
D1370N
site-directed mutagenesis of a conserved residue in the Walker B motif of ATP-binding site 2, the mutation abolishes P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
Homo sapiens
5.6.1.6
D572N
site-directed mutagenesis of a conserved residue in the Walker B motif of ATP-binding site 1, the mutation does not abolish P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
Homo sapiens
5.6.1.6
K1250A
site-directed mutagenesis of a conserved residue in the Walker A motif of ATP-binding site 2, the mutation abolishes P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
Homo sapiens
5.6.1.6
K464A
site-directed mutagenesis of a conserved residue in the Walker A motif of ATP-binding site 1, the mutation does not abolish P1,P5-di(adenosine-5') pentaphosphate, Ap5A, inhibition of current
Homo sapiens
5.6.1.6
additional information
photolabeling of CFTR with 8-N3-[32P]AMP or 8-N3-[32P]ATP
Homo sapiens
5.6.1.6
S1248F
site-directed mutagenesis, the mutation abolishes nucleotide interaction with ATP-binding site 2, the mutant exhibits a low, ATP-dependent open probability due to a reduced opening rate with a normal burst duration. The S1248F mutation does not interfere with processing and trafficking to the cell membrane
Homo sapiens
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
2.7.4.3
P1,P4-di(adenosine-5') tetraphosphate
Ap4A
Homo sapiens
2.7.4.3
P1,P5-di(adenosine-5') pentaphosphate
Ap5A, interacts simultaneously with an AMP-binding site and ATP-binding site 2
Homo sapiens
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
5.6.1.6
membrane
-
Homo sapiens
16020
-
Metals/Ions (protein specific)
EC Number
Metals/Ions
Commentary
Organism
Structure
2.7.4.3
Mg2+
required
Homo sapiens
5.6.1.6
Mg2+
required
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2.7.4.3
ATP + AMP
Homo sapiens
-
2 ADP
-
-
r
2.7.4.3
additional information
Homo sapiens
the cystic fibrosis transmembrane conductance regulator (CFTR) has adenylate kinase activity as an ABC adenylate kinase. ATP enables CFTR photolabeling by 8-N3-AMP, and AMP increases 8-N3-ATP photolabeling at ATP-binding site 2. AMP interacts with CFTR in an ATP-dependent manner and alters ATP interaction with the adenylate kinase active center ATP-binding site. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, also have adenylate kinase activity. All three ABC adenylate kinases bind and hydrolyze ATP in the absence of other nucleotides
?
-
-
-
5.6.1.6
ATP + H2O + closed Cl- channel
Homo sapiens
-
ADP + phosphate + open Cl- channel
-
-
?
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.7.4.3
ATP + AMP
-
734231
Homo sapiens
2 ADP
-
-
-
r
2.7.4.3
additional information
the cystic fibrosis transmembrane conductance regulator (CFTR) has adenylate kinase activity as an ABC adenylate kinase. ATP enables CFTR photolabeling by 8-N3-AMP, and AMP increases 8-N3-ATP photolabeling at ATP-binding site 2. AMP interacts with CFTR in an ATP-dependent manner and alters ATP interaction with the adenylate kinase active center ATP-binding site. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, also have adenylate kinase activity. All three ABC adenylate kinases bind and hydrolyze ATP in the absence of other nucleotides
734231
Homo sapiens
?
-
-
-
-
5.6.1.6
ATP + H2O + closed Cl- channel
-
734231
Homo sapiens
ADP + phosphate + open Cl- channel
-
-
-
?
5.6.1.6
additional information
in the presence of ATP and physiologically relevant concentrations of AMP, the enzyme exhibits adenylate kinase activity, converting ATP and AMP into 2 ADP and vice versa. The interaction of nucleotide triphosphate with the enzyme at ATP-binding site 2 is required for this activity. ATP and AMP interact with separate binding sites but mutually influence their interaction with the ABC adenylate kinase CFTR, the active center of the adenylate kinase comprises ATP-binding site 2
734231
Homo sapiens
?
-
-
-
-
Subunits (protein specific)
EC Number
Subunits
Commentary
Organism
5.6.1.6
More
construction of a putative molecular three-dimensional model of the nucleotide-binding domain 1-nucleotide-binding domain 2 heterodimer
Homo sapiens
Temperature Optimum [°C] (protein specific)
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
5.6.1.6
23
26
assay at room temperature
Homo sapiens
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
2.7.4.3
7.5
-
assay at
Homo sapiens
5.6.1.6
7.3
-
assay at
Homo sapiens
General Information
EC Number
General Information
Commentary
Organism
2.7.4.3
additional information
ATP and AMP interact with separate binding sites but mutually influence their interaction with the ABC adenylate kinase CFTR. The active center of an adenylate kinase comprises separate ATP- and AMP-binding sites, and comprises ATP-binding site 2. Construction of a three-dimensional model of the CFTR NBD1-NBD2 heterodimer, molecular modelling with bound ATP molecules, overview
Homo sapiens
5.6.1.6
evolution
the enzyme is an ATP-binding cassette (ABC) adenylate kinase and anion channel in the ATP-binding cassette (ABC) transporter protein family
Homo sapiens
5.6.1.6
additional information
photolabeling of CFTR with 8-N3-[32P]AMP or 8-N3-[32P]ATP, with a photoactivatable azido (N3)-group attached to the adenine ring, the photolabeling is enhanced by AMP and inhibited by P1,P4-di(adenosine-5') tetraphosphate and P1,P5-di(adenosine-5') pentaphosphate, which do not interact with all CFTR ATP-binding sites. Specific labeling of an AMP-binding site in the presence of ATP. Construction of a putative molecular three-dimensional model of the nucleotide-binding domain 1-nucleotide-binding domain 2 heterodimer, the crystal structure of NBD1 in complex with ATP (PDB code 1R0X) is used as template for constructing a homology model of NBD2
Homo sapiens
5.6.1.6
physiological function
the enzyme is an ATP-binding cassette adenylate kinase and anion channel
Homo sapiens
General Information (protein specific)
EC Number
General Information
Commentary
Organism
2.7.4.3
additional information
ATP and AMP interact with separate binding sites but mutually influence their interaction with the ABC adenylate kinase CFTR. The active center of an adenylate kinase comprises separate ATP- and AMP-binding sites, and comprises ATP-binding site 2. Construction of a three-dimensional model of the CFTR NBD1-NBD2 heterodimer, molecular modelling with bound ATP molecules, overview
Homo sapiens
5.6.1.6
evolution
the enzyme is an ATP-binding cassette (ABC) adenylate kinase and anion channel in the ATP-binding cassette (ABC) transporter protein family
Homo sapiens
5.6.1.6
additional information
photolabeling of CFTR with 8-N3-[32P]AMP or 8-N3-[32P]ATP, with a photoactivatable azido (N3)-group attached to the adenine ring, the photolabeling is enhanced by AMP and inhibited by P1,P4-di(adenosine-5') tetraphosphate and P1,P5-di(adenosine-5') pentaphosphate, which do not interact with all CFTR ATP-binding sites. Specific labeling of an AMP-binding site in the presence of ATP. Construction of a putative molecular three-dimensional model of the nucleotide-binding domain 1-nucleotide-binding domain 2 heterodimer, the crystal structure of NBD1 in complex with ATP (PDB code 1R0X) is used as template for constructing a homology model of NBD2
Homo sapiens
5.6.1.6
physiological function
the enzyme is an ATP-binding cassette adenylate kinase and anion channel
Homo sapiens