Application | Comment | Organism |
---|---|---|
medicine | the enzyme is a promising and attractive target for cancer treatment | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(5Z)-5-(2,3,4-trihydroxybenzylidene)-1,3-thiazolidine-2,4-dithione | - |
Homo sapiens | |
2-(3-(dimethylamino)propoxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione | - |
Homo sapiens | |
2-(3-(ethylamino)propoxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione | - |
Homo sapiens | |
2-(3-aminopropoxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione | - |
Homo sapiens | |
3-methoxy-6-(3-morpholinopropyl)-2-(3-(piperidin-1-yl)-propoxy)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione | - |
Homo sapiens | |
3-methoxy-6-(3-morpholinopropyl)-2-(3-(pyrrolidin-1-yl)-propoxy)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione | - |
Homo sapiens | |
6,6'-[propane-1,3-diylbis(iminopropane-3,1-diyl)]bis(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 | |
furamidine | - |
Homo sapiens | |
additional information | structure-based drug design, synthesis, and biological evaluation of O-2-modified indenoisoquinolines as dual topoisomerase I-tyrosyl-DNA phosphodiesterase I inhibitors, structure-activity relationships, molecular docking studies, and molecular modeling, overview. No inhibition by 2-(allyloxy)-3-methoxy-6-(3-morpholinopropyl)-5H-[1,3]-dioxolo[4',5':5,6]indeno [1,2-c]isoquinoline-5,12(6H)-dione, 3-methoxy-2-(3-morpholinopropoxy)-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione, 3-methoxy-2-(3-(4-methylpiperazin-1-yl)propoxy)-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]-isoquinoline-5,12(6H)-dione, methyl 2-((3-methoxy-6-(3-morpholinopropyl)-5,12-dioxo-6,12-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]-isoquinolin-2-yl)oxy)acetate, and 2-((12-hydroxy-3-methoxy-6-(3-morpholinopropyl)-5-oxo-6,12-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]-isoquinolin-2-yl)oxy)acetohydrazide. Antiproliferative potencies of selected O-2-modified indenoisoquinolines, overview | Homo sapiens | |
NSC88915 | a steroid inhibitor | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | the enzyme catalyzes the hydrolysis of 3' phosphotyrosyl linkers and other 3'-end blocking lesions. When Top1 nicks double-stranded DNA, a covalent cleavage complex is formed that can be repaired by the enzyme, the mechanism involves the following steps: first, as Lys265 and Lys495 residues in the catalytic site coordinate the oxygen atoms of the phosphate group, His263 attacks the phosphorus atom linked to the oxygen of the Top1 catalytic residue, Tyr723, at the 3' end of DNA. Second, the TDP1-DNA covalent intermediate formed is hydrolyzed by a His493-activated water molecule, leading to the generation of a DNA product with a 3' phosphate | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | the enzyme catalyzes the hydrolysis of 3' phosphotyrosyl linkers and other 3'-end blocking lesions. When Top1 nicks double-stranded DNA, a covalent cleavage complex is formed that can be repaired by the enzyme, the mechanism involves the following steps: first, as Lys265 and Lys495 residues in the catalytic site coordinate the oxygen atoms of the phosphate group, His263 attacks the phosphorus atom linked to the oxygen of the Top1 catalytic residue, Tyr723, at the 3' end of DNA. Second, the TDP1-DNA covalent intermediate formed is hydrolyzed by a His493-activated water molecule, leading to the generation of a DNA product with a 3' phosphate | Homo sapiens | ? | - |
? | |
additional information | substrate is a 5'-[32P]-labeled single-stranded DNA oligonucleotide containing a 3' phosphotyrosine (N14Y) | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
TDP1 | - |
Homo sapiens |
tyrosyl-DNA phosphodiesterase I | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
22 | - |
assay at room temperature | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
evolution | tyrosyl-DNA phosphodiesterase I is a member of the phospholipase D superfamily of enzymes | Homo sapiens |
physiological function | the enzyme plays a critical role in the cellular repair of topoisomerase 1-mediated DNA damage | Homo sapiens |