Inhibitors | Comment | Organism | Structure |
---|---|---|---|
6,6'-[propane-1,3-diylbis(iminopropane-3,1-diyl)]bis(5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione) | - |
Homo sapiens | |
6-(10-aminodecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(11-aminoundecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(12-aminododecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(2-aminoethyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(4-aminobutyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(5-aminopentyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(6-aminohexyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(7-aminoheptyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(8-aminooctyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
6-(9-aminononyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | - |
Homo sapiens | |
furamidine | - |
Homo sapiens | |
additional information | synthesis and evaluation of dual tyrosyl-DNA phosphodiesterase I-topoisomerase I inhibitors based on the indenoisoquinoline chemotype, structure-activity relationship studies, overview | Homo sapiens | |
neomycin B | a aminoglycoside | Homo sapiens | |
NSC 88915 | a steroid inhibitor | Homo sapiens | |
sodium orthovanadate | - |
Homo sapiens | |
tungstate | - |
Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | tyrosyl-DNA phosphodiesterase I specifically catalyzes the hydrolysis of the phosphodiester bond between the catalytic Tyr723 of Top1 and DNA-3'-phosphate, then polynucleotide kinase phosphatase hydrolyzes the resulting 3'-phosphate end and catalyzes the phosphorylation of the 5'-hydroxyl end of the broken DNA strand. This results in a broken DNA strand with termini consisting of a 5'-phosphate and 3'-hydroxyl for DNA repair. DNA polymerase beta replaces the missing DNA segment, and finally DNA ligase III reseals the broken DNA | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | tyrosyl-DNA phosphodiesterase I specifically catalyzes the hydrolysis of the phosphodiester bond between the catalytic Tyr723 of Top1 and DNA-3'-phosphate, then polynucleotide kinase phosphatase hydrolyzes the resulting 3'-phosphate end and catalyzes the phosphorylation of the 5'-hydroxyl end of the broken DNA strand. This results in a broken DNA strand with termini consisting of a 5'-phosphate and 3'-hydroxyl for DNA repair. DNA polymerase beta replaces the missing DNA segment, and finally DNA ligase III reseals the broken DNA | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | the enzyme is composed of two domains related by a pseudo-twofold axis of symmetry. Each domain contributes a histidine and a lysine residue to form an active site that is centrally located at the symmetry axis | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
TDP1 | - |
Homo sapiens |
tyrosyl-DNA phosphodiesterase I | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00152 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6,6'-[propane-1,3-diylbis(iminopropane-3,1-diyl)]bis(5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione) | |
0.0128 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(11-aminoundecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.014 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(10-aminodecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.0151 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(12-aminododecyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.0175 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(5-aminopentyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.0223 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(4-aminobutyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.025 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(6-aminohexyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.0288 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(7-aminoheptyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.0295 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.047 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(9-aminononyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.048 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(8-aminooctyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione | |
0.0553 | - |
pH 7.5, 25°C, recombinant enzyme | Homo sapiens | 6-(2-aminoethyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione |
General Information | Comment | Organism |
---|---|---|
evolution | the enzyme is a member of the phospholipase D superfamily of enzymes that catalyze the hydrolysis of a variety of phosphodiester bonds in many different substrates | Homo sapiens |
metabolism | the tyrosyl-DNA phosphodiesterase I hydrolyzes the phosphotyrosyl linkage between degraded Top1 and DNA, then polynucleotide kinase phosphatase hydrolyzes the resulting 3'-phosphate end and catalyzes the phosphorylation of the 5'-hydroxyl end of the broken DNA strand. This results in a broken DNA strand with termini consisting of a 5'-phosphate and 3'-hydroxyl for DNA repair. DNA polymerase beta replaces the missing DNA segment, and finally DNA ligase III reseals the broken DNA. Tyrosyl-DNA phosphodiesterase I is the only enzyme that specifically catalyzes the hydrolysis of the phosphodiester bond between the catalytic Tyr723 of Top1 and DNA-3'-phosphate | Homo sapiens |
additional information | the enzyme is composed of two domains related by a pseudo-twofold axis of symmetry. Each domain contributes a histidine and a lysine residue to form an active site that is centrally located at the symmetry axis. Four additional residues N283, Q294, N516, and E538 are also positioned near the active site | Homo sapiens |