Protein Variants | Comment | Organism |
---|---|---|
Y505A | N-[6-N-(2,4-dinitrophenyl)aminohexanoyl]-2-aminoethyl triphosphate, N-(2,4-dinitro-5-fluorophenyl)-2-aminoethyl triphosphate, N-(2,4-dinitro-5-imidazolylphenyl)-4-aminobutyl triphosphate and N-(2,4-dinitro-5-imidazolylphenyl)-2-aminoethyl triphosphate inhibit mutant enzyme Y505A and are inactive against wild-type enzyme. DNA polymerase lambda and its mutant Y505A show different abilities of incorporating NNTPs in the presence of an abasic site on the template strand | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(9-adenylmethylcarbonyl)-4-aminobutyl triphosphate | fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A | Homo sapiens | |
(biphenylcarbonyl)-4-oxobutyl triphosphate | fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A; inhibits wild-type enzyme and mutant enzyme Y505A | Homo sapiens | |
2-thiomethyl-6-phenyl-4-(4'-hydroxybutyl)-1,2,4,-triazole (5,1-C)(1,2,4)triazine-7-one triphosphate | fully competitive with respect to the nucleotide substrate dTTP; fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A | Homo sapiens | |
additional information | no inhibition by (9-adenylmethylcarbonyl)-4-aminobutyl, N-(2,4-dinitrophenyl)-4-aminobutyl triphosphate, N-(2,4-dinitro-5-fluorophenyl)-4-aminobutyl triphosphate, N-[6-N-(2,4-dinitrophenyl)aminohexanoyl]-2-aminoethyl triphosphate, N-(2,4-dinitro-5-fluorophenyl)-2-aminoethyl triphosphate, N-(2,4-dinitro-5-imidazolylphenyl)-4-aminobutyl triphosphate and N-(2,4-dinitro-5-imidazolylphenyl)-2-aminoethyl triphosphate | Homo sapiens | |
N-(2,4-dinitro-5-fluorophenyl)-2-aminoethyl triphosphate | inhibition of mutant enzyme Y505A, inactive against wild-type enzyme | Homo sapiens | |
N-(2,4-dinitro-5-fluorophenyl)-4-aminobutyl triphosphate | fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A | Homo sapiens | |
N-(2,4-dinitro-5-imidazolylphenyl)-2-aminoethyl triphosphate | inhibition of mutant enzyme Y505A, inactive against wild-type enzyme | Homo sapiens | |
N-(2,4-dinitro-5-imidazolylphenyl)-4-aminobutyl triphosphate | inhibition of mutant enzyme Y505A, inactive against wild-type enzyme | Homo sapiens | |
N-(2,4-dinitrophenyl)-4-aminobutyl triphosphate | fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A | Homo sapiens | |
N-(benzyloxycarbonyl)-4-aminobutyl triphosphate | fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A; inhibits wild-type enzyme and mutant enzyme Y505A | Homo sapiens | |
N-[6-N-(2,4-dinitrophenyl)aminohexanoyl]-2-aminoethyl triphosphate | inhibition of mutant enzyme Y505A, inactive against wild-type enzyme | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | poly(dA)/oligo(dT)10:1. In the presence of Mn2+, DNA polymerase beta incorporates (biphenylcarbonyl)-4-oxobutyl triphosphate both on an intact template and opposite to an abasic site. DNA polymerase beta incorporates dCTP on the undamaged template, whereas it exclusively incorporates dATP opposite the abasic site. The incorporation efficiency of (biphenylcarbonyl)-4-oxobutyl triphosphate by DNA polymerase beta is 2fold higher in the presence of the undamaged template, with respect to the one carrying an abasic site. When Mn2+ is replaced by Mg2+, this difference becomes even more striking, so that (biphenylcarbonyl)-4-oxobutyl triphosphate can be exclusively incorporated on the undamaged in the presence of Mg2+, the incorporation of (biphenylcarbonyl)-4-oxobutyl triphosphate by DNA polymerase beta becomes strictly dependent on the presence of a templating base. Replacement of Mn2+ with Mg2+, however, greatly enhances the preference for incorporation of dCTP versus (biphenylcarbonyl)-4-oxobutyl triphosphate opposite a template G by DNA polymerase beta, which increases from 23fold to 239fold | Homo sapiens | |
Mn2+ | incorporation of the NNTPs is observed only in the presence of its optimal activator, Mn2+ | Homo sapiens | |
Mn2+ | poly(dA)/oligo(dT)10:1. In the presence of Mn2+, DNA polymerase beta incorporates (biphenylcarbonyl)-4-oxobutyl triphosphate both on an intact template and opposite to an abasic site. DNA polymerase beta incorporates dCTP on the undamaged template, whereas it exclusively incorporates dATP opposite the abasic site. The incorporation efficiency of (biphenylcarbonyl)-4-oxobutyl triphosphate by DNA polymerase beta is 2fold higher in the presence of the undamaged template, with respect to the one carrying an abasic site. When Mn2+ is replaced by Mg2+, this difference becomes even more striking, so that (biphenylcarbonyl)-4-oxobutyl triphosphate can be exclusively incorporated on the undamaged in the presence of Mg2+, the incorporation of (biphenylcarbonyl)-4-oxobutyl triphosphate by DNA polymerase beta becomes strictly dependent on the presence of a templating base. Replacement of Mn2+ with Mg2+, however, greatly enhances the preference for incorporation of dCTP versus (biphenylcarbonyl)-4-oxobutyl triphosphate opposite a template G by DNA polymerase beta, which increases from 23fold to 239fold | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Purification (Comment) | Organism |
---|---|
- |
Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
deoxynucleoside triphosphate + DNAn | poly(dA)/oligo(dT)10:1. 2-thiomethyl-6-phenyl-4-(4'-hydroxybutyl)-1,2,4,-triazole (5,1-C)(1,2,4)triazine-7-one triphosphate can be incorporated on both templates but only by the Y505A mutant enzyme. N-(Benzyloxycarbonyl)-4-aminobutyl triphosphate can be incorporated by DNA pol lambda either wild type or the Y505A mutant, opposite to an abasic site only. Incorporation efficiency of (biphenylcarbonyl)-4-oxobutyl triphosphate by DNA polymmerase lambda wild type is 22fold higher opposite an abasic site than on the intact template. DNA polymerase lambda wild type incorporates (biphenylcarbonyl)-4-oxobutyl triphosphate 2.2fold more frequently than dCTP opposite the lesion. The DNA polymerase lambda Y505A mutant shows a 5.3fold preference for dCTP versus (biphenylcarbonyl)-4-oxobutyl triphosphate incorporation opposite the lesion | Homo sapiens | diphosphate + DNAn+1 | - |
? | |
deoxynucleoside triphosphate + DNAn | poly(dA)/oligo(dT)10:1. In the presence of Mn2+, DNA polymerase beta incorporates (biphenylcarbonyl)-4-oxobutyl triphosphate both on an intact template and opposite to an abasic site. DNA polymerase beta incorporates dCTP on the undamaged template, whereas it exclusively incorporates dATP opposite the abasic site. The incorporation efficiency of (biphenylcarbonyl)-4-oxobutyl triphosphate by DNA polymerase beta is 2fold higher in the presence of the undamaged template, with respect to the one carrying an abasic site. When Mn2+ is replaced by Mg2+, this difference becomes even more striking, so that (biphenylcarbonyl)-4-oxobutyl triphosphate can be exclusively incorporated on the undamaged in the presence of Mg2+, the incorporation of (biphenylcarbonyl)-4-oxobutyl triphosphate by DNA polymerase beta becomes strictly dependent on the presence of a templating base. Replacement of Mn2+ with Mg2+, however, greatly enhances the preference for incorporation of dCTP versus (biphenylcarbonyl)-4-oxobutyl triphosphate opposite a template G by DNA polymerase beta, which increases from 23fold to 239fold | Homo sapiens | diphosphate + DNAn+1 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
DNA polymerase beta | - |
Homo sapiens |
DNA polymerase lambda | - |
Homo sapiens |
pol beta | - |
Homo sapiens |
Pol lambda | - |
Homo sapiens |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0004 | - |
(biphenylcarbonyl)-4-oxobutyl triphosphate | 37°C, pH 7.0, mutant enzyme Y505A | Homo sapiens | |
0.0005 | - |
N-(2,4-dinitro-5-imidazolylphenyl)-2-aminoethyl triphosphate | mutant enzyme Y505A | Homo sapiens | |
0.0011 | - |
(biphenylcarbonyl)-4-oxobutyl triphosphate | 37°C, pH 7.0, wild-type enzyme | Homo sapiens | |
0.0012 | - |
N-(2,4-dinitrophenyl)-4-aminobutyl triphosphate | 37°C, pH 7.0, wild-type enzyme | Homo sapiens | |
0.0016 | - |
N-(benzyloxycarbonyl)-4-aminobutyl triphosphate | 37°C, pH 7.0, mutant enzyme Y505A | Homo sapiens | |
0.0017 | - |
N-(benzyloxycarbonyl)-4-aminobutyl triphosphate | 37°C, pH 7.0, wild-type enzyme | Homo sapiens | |
0.0018 | - |
2-thiomethyl-6-phenyl-4-(4'-hydroxybutyl)-1,2,4,-triazole (5,1-C)(1,2,4)triazine-7-one triphosphate | 37°C, pH 7.0, mutant enzyme Y505A | Homo sapiens | |
0.0027 | - |
2-thiomethyl-6-phenyl-4-(4'-hydroxybutyl)-1,2,4,-triazole (5,1-C)(1,2,4)triazine-7-one triphosphate | 37°C, pH 7.0, wid-type enzyme | Homo sapiens | |
0.0028 | - |
(9-adenylmethylcarbonyl)-4-aminobutyl triphosphate | 37°C, pH 7.0, wild-type enzyme | Homo sapiens | |
0.0031 | - |
N-(2,4-dinitro-5-fluorophenyl)-4-aminobutyl triphosphate | 37°C, pH 7.0, wild-type enzyme | Homo sapiens | |
0.0035 | - |
N-(2,4-dinitrophenyl)-4-aminobutyl triphosphate | 37°C, pH 7.0, mutant enzyme Y505A | Homo sapiens | |
0.0038 | - |
(9-adenylmethylcarbonyl)-4-aminobutyl triphosphate | 37°C, pH 7.0, mutant enzyme Y505A | Homo sapiens | |
0.0048 | - |
(biphenylcarbonyl)-4-oxobutyl triphosphate | 37°C, pH 7.0, wild-type enzyme | Homo sapiens | |
0.0065 | - |
N-(2,4-dinitro-5-fluorophenyl)-4-aminobutyl triphosphate | 37°C, pH 7.0, mutant enzyme Y505A | Homo sapiens | |
0.0091 | - |
N-[6-N-(2,4-dinitrophenyl)aminohexanoyl]-2-aminoethyl triphosphate | mutant enzyme Y505A | Homo sapiens | |
0.0144 | - |
N-(2,4-dinitro-5-fluorophenyl)-2-aminoethyl triphosphate | mutant enzyme Y505A | Homo sapiens | |
0.0154 | - |
N-(2,4-dinitro-5-imidazolylphenyl)-4-aminobutyl triphosphate | mutant enzyme Y505A | Homo sapiens | |
0.068 | - |
2-thiomethyl-6-phenyl-4-(4'-hydroxybutyl)-1,2,4,-triazole (5,1-C)(1,2,4)triazine-7-one triphosphate | 37°C, pH 7.0, wid-type enzyme | Homo sapiens | |
0.07 | - |
N-(benzyloxycarbonyl)-4-aminobutyl triphosphate | 37°C, pH 7.0, wild-type enzyme | Homo sapiens |