Literature summary for 2.7.7.7 extracted from

Crespan, E.; Alexandrova, L.; Khandazhinskaya, A.; Jasko, M.; Kukhanova, M.; Villani, G.; Huebscher, U.; Spadari, S.; Maga, G.
Expanding the repertoire of DNA polymerase substrates: template-instructed incorporation of non-nucleoside triphosphate analogues by DNA polymerases beta and lambda (2007), Nucleic Acids Res., 35, 45-57.

Search for more literature for 2.7.7.7

Protein Variants

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

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

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

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
-	Homo sapiens

Substrates and Products (Substrate)

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

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 [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

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Release 2023.1 (January 2023)