BRENDA - Enzyme Database show

Structural basis for the preference of UTP over ATP in human deoxycytidine kinase: Illuminating the role of main-chain reorganization

Godsey, M.H.; Ort, S.; Sabini, E.; Konrad, M.; Lavie, A.; Biochemistry 45, 452-461 (2006)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
2.7.1.74
expressed of engineered protein as His-tag fusion protein in Escherichia coli
Homo sapiens
Crystallization (Commentary)
EC Number
Crystallization
Organism
2.7.1.74
hanging drop vapour diffusion method, in complex with deoxycytidine (dC) and UDP, and in the presence of deoxycytidine but the absence of UDP or ADP
Homo sapiens
Engineering
EC Number
Amino acid exchange
Commentary
Organism
2.7.1.74
DEL65-79
construction of an enzyme variant lacking a flexible insert (residues 65-79) but having similar catalytic properties as the wild type
Homo sapiens
KM Value [mM]
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
2.7.1.74
0.001
-
2'-deoxycytidine
less than 0.001 mM, residues 65-79 deletion mutant with UTP as cosubstrate; less than 0.001 mM, wild type enzyme with ATP as cosubstrate; less than 0.001 mM, wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.0014
-
2'-deoxycytidine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.0015
-
UTP
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.0023
-
UTP
wild type enzyme deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.0029
-
ATP
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.003
-
1-beta-D-arabinofuranosylcytosine
residues 65-79 deletion mutant with UTP as cosubstrate; wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.0035
-
ATP
wild type enzyme with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.0047
-
UTP
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.007
-
1-beta-D-arabinofuranosylcytosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.01
-
UTP
wild type enzyme deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.013
-
1-beta-D-arabinofuranosylcytosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.013
-
2'-deoxyadenosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.021
-
2'-deoxyguanosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.053
-
2'-deoxyadenosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.053
-
ATP
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.087
-
2'-deoxyguanosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.093
-
ATP
wild type enzyme with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.1
-
2'-deoxyadenosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.231
-
2'-deoxyguanosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.415
-
2'-deoxyadenosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.474
-
2'-deoxyguanosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
Molecular Weight [Da]
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
2.7.1.74
30500
-
2 * 30500, calculated from the deduced amino acid sequence, crystal structure analysis
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2.7.1.74
NTP + 1-beta-D-arabinofuranosylcytosine
Homo sapiens
antineoplastic agent
NDP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2',3'-dideoxycytidine
Homo sapiens
antiviral agent
NDP + 2',3'-dideoxycytidine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2'-deoxy-3'-thiacytidine
Homo sapiens
antiviral agent
NDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2'-deoxyadenosine
Homo sapiens
rate-limiting reaction in the salvage of deoxyribonucleosides
NDP + 2'-deoxyadenosine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2'-deoxycytidine
Homo sapiens
rate-limiting reaction in the salvage of deoxyribonucleosides
NDP + 2'-deoxycytidine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2'-deoxyguanosine
Homo sapiens
rate-limiting reaction in the salvage of deoxyribonucleosides
NDP + 2'-deoxyguanosine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2-chloro-2'-deoxyadenosine
Homo sapiens
i.e. cladribine, antineoplastic agent
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
2.7.1.74
Homo sapiens
P27707
-
-
Purification (Commentary)
EC Number
Commentary
Organism
2.7.1.74
recombinant protein using His-tag
Homo sapiens
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.7.1.74
NTP + 1-beta-D-arabinofuranosylcytosine
antineoplastic agent
672149
Homo sapiens
NDP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2',3'-dideoxycytidine
antiviral agent
672149
Homo sapiens
NDP + 2',3'-dideoxycytidine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2'-deoxy-3'-thiacytidine
antiviral agent
672149
Homo sapiens
NDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2'-deoxyadenosine
rate-limiting reaction in the salvage of deoxyribonucleosides
672149
Homo sapiens
NDP + 2'-deoxyadenosine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2'-deoxycytidine
rate-limiting reaction in the salvage of deoxyribonucleosides
672149
Homo sapiens
NDP + 2'-deoxycytidine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2'-deoxyguanosine
rate-limiting reaction in the salvage of deoxyribonucleosides
672149
Homo sapiens
NDP + 2'-deoxyguanosine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2-chloro-2'-deoxyadenosine
i.e. cladribine, antineoplastic agent
672149
Homo sapiens
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
-
-
-
?
Subunits
EC Number
Subunits
Commentary
Organism
2.7.1.74
dimer
2 * 30500, calculated from the deduced amino acid sequence, crystal structure analysis
Homo sapiens
Turnover Number [1/s]
EC Number
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
2.7.1.74
0.028
-
ATP
wild type enzyme with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.031
-
UTP
wild type enzyme deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.033
-
2'-deoxycytidine
less than 0.001 mM, wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.039
-
ATP
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.041
-
UTP
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.044
-
2'-deoxycytidine
less than 0.001 mM, wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.049
-
2'-deoxycytidine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.075
-
UTP
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.088
-
2'-deoxycytidine
less than 0.001 mM, residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.093
-
UTP
wild type enzyme deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.15
-
1-beta-D-arabinofuranosylcytosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.17
-
1-beta-D-arabinofuranosylcytosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.3
-
1-beta-D-arabinofuranosylcytosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.31
-
2'-deoxyadenosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.32
-
2'-deoxyguanosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.33
-
2'-deoxyadenosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.33
-
2'-deoxyguanosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.36
-
ATP
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.4
-
ATP
wild type enzyme with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.41
-
1-beta-D-arabinofuranosylcytosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
1.7
-
2'-deoxyadenosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
2.2
-
2'-deoxyguanosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
2.6
-
2'-deoxyguanosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
2.8
-
2'-deoxyadenosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
Cofactor
EC Number
Cofactor
Commentary
Organism
Structure
2.7.1.74
ATP
-
Homo sapiens
2.7.1.74
UTP
preferred phosphoryl group donor
Homo sapiens
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
2.7.1.74
expressed of engineered protein as His-tag fusion protein in Escherichia coli
Homo sapiens
Cofactor (protein specific)
EC Number
Cofactor
Commentary
Organism
Structure
2.7.1.74
ATP
-
Homo sapiens
2.7.1.74
UTP
preferred phosphoryl group donor
Homo sapiens
Crystallization (Commentary) (protein specific)
EC Number
Crystallization
Organism
2.7.1.74
hanging drop vapour diffusion method, in complex with deoxycytidine (dC) and UDP, and in the presence of deoxycytidine but the absence of UDP or ADP
Homo sapiens
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
2.7.1.74
DEL65-79
construction of an enzyme variant lacking a flexible insert (residues 65-79) but having similar catalytic properties as the wild type
Homo sapiens
KM Value [mM] (protein specific)
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
2.7.1.74
0.001
-
2'-deoxycytidine
less than 0.001 mM, residues 65-79 deletion mutant with UTP as cosubstrate; less than 0.001 mM, wild type enzyme with ATP as cosubstrate; less than 0.001 mM, wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.0014
-
2'-deoxycytidine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.0015
-
UTP
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.0023
-
UTP
wild type enzyme deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.0029
-
ATP
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.003
-
1-beta-D-arabinofuranosylcytosine
residues 65-79 deletion mutant with UTP as cosubstrate; wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.0035
-
ATP
wild type enzyme with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.0047
-
UTP
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.007
-
1-beta-D-arabinofuranosylcytosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.01
-
UTP
wild type enzyme deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.013
-
1-beta-D-arabinofuranosylcytosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.013
-
2'-deoxyadenosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.021
-
2'-deoxyguanosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.053
-
2'-deoxyadenosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.053
-
ATP
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.087
-
2'-deoxyguanosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.093
-
ATP
wild type enzyme with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.1
-
2'-deoxyadenosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.231
-
2'-deoxyguanosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.415
-
2'-deoxyadenosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.474
-
2'-deoxyguanosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
Molecular Weight [Da] (protein specific)
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
2.7.1.74
30500
-
2 * 30500, calculated from the deduced amino acid sequence, crystal structure analysis
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
2.7.1.74
NTP + 1-beta-D-arabinofuranosylcytosine
Homo sapiens
antineoplastic agent
NDP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2',3'-dideoxycytidine
Homo sapiens
antiviral agent
NDP + 2',3'-dideoxycytidine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2'-deoxy-3'-thiacytidine
Homo sapiens
antiviral agent
NDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2'-deoxyadenosine
Homo sapiens
rate-limiting reaction in the salvage of deoxyribonucleosides
NDP + 2'-deoxyadenosine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2'-deoxycytidine
Homo sapiens
rate-limiting reaction in the salvage of deoxyribonucleosides
NDP + 2'-deoxycytidine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2'-deoxyguanosine
Homo sapiens
rate-limiting reaction in the salvage of deoxyribonucleosides
NDP + 2'-deoxyguanosine 5'-phosphate
-
-
?
2.7.1.74
NTP + 2-chloro-2'-deoxyadenosine
Homo sapiens
i.e. cladribine, antineoplastic agent
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
-
-
?
Purification (Commentary) (protein specific)
EC Number
Commentary
Organism
2.7.1.74
recombinant protein using His-tag
Homo sapiens
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.7.1.74
NTP + 1-beta-D-arabinofuranosylcytosine
antineoplastic agent
672149
Homo sapiens
NDP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2',3'-dideoxycytidine
antiviral agent
672149
Homo sapiens
NDP + 2',3'-dideoxycytidine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2'-deoxy-3'-thiacytidine
antiviral agent
672149
Homo sapiens
NDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2'-deoxyadenosine
rate-limiting reaction in the salvage of deoxyribonucleosides
672149
Homo sapiens
NDP + 2'-deoxyadenosine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2'-deoxycytidine
rate-limiting reaction in the salvage of deoxyribonucleosides
672149
Homo sapiens
NDP + 2'-deoxycytidine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2'-deoxyguanosine
rate-limiting reaction in the salvage of deoxyribonucleosides
672149
Homo sapiens
NDP + 2'-deoxyguanosine 5'-phosphate
-
-
-
?
2.7.1.74
NTP + 2-chloro-2'-deoxyadenosine
i.e. cladribine, antineoplastic agent
672149
Homo sapiens
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
-
-
-
?
Subunits (protein specific)
EC Number
Subunits
Commentary
Organism
2.7.1.74
dimer
2 * 30500, calculated from the deduced amino acid sequence, crystal structure analysis
Homo sapiens
Turnover Number [1/s] (protein specific)
EC Number
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
2.7.1.74
0.028
-
ATP
wild type enzyme with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.031
-
UTP
wild type enzyme deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.033
-
2'-deoxycytidine
less than 0.001 mM, wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.039
-
ATP
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.041
-
UTP
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
Homo sapiens
2.7.1.74
0.044
-
2'-deoxycytidine
less than 0.001 mM, wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.049
-
2'-deoxycytidine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.075
-
UTP
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.088
-
2'-deoxycytidine
less than 0.001 mM, residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.093
-
UTP
wild type enzyme deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.15
-
1-beta-D-arabinofuranosylcytosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.17
-
1-beta-D-arabinofuranosylcytosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.3
-
1-beta-D-arabinofuranosylcytosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
0.31
-
2'-deoxyadenosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.32
-
2'-deoxyguanosine
residues 65-79 deletion mutant with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.33
-
2'-deoxyadenosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.33
-
2'-deoxyguanosine
wild type enzyme with UTP as cosubstrate
Homo sapiens
2.7.1.74
0.36
-
ATP
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.4
-
ATP
wild type enzyme with 1-beta-D-arabinofuranosylcytosine as cosubstrate
Homo sapiens
2.7.1.74
0.41
-
1-beta-D-arabinofuranosylcytosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
1.7
-
2'-deoxyadenosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
2.2
-
2'-deoxyguanosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens
2.7.1.74
2.6
-
2'-deoxyguanosine
wild type enzyme with ATP as cosubstrate
Homo sapiens
2.7.1.74
2.8
-
2'-deoxyadenosine
residues 65-79 deletion mutant with ATP as cosubstrate
Homo sapiens