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Literature summary for 3.1.4.1 extracted from

  • Nguyen, T.X.; Morrell, A.; Conda-Sheridan, M.; Marchand, C.; Agama, K.; Bermingham, A.; Bermingam, A.; Stephen, A.G.; Chergui, A.; Naumova, A.; Fisher, R.; OKeefe, B.R.; Pommier, Y.; Cushman, M.
    Synthesis and biological evaluation of the first dual tyrosyl-DNA phosphodiesterase I (Tdp1)-topoisomerase I (Top1) inhibitors (2012), J. Med. Chem., 55, 4457-4478.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.1.4.1

Inhibitors

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

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

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

Synonyms Comment Organism
TDP1
-
 Homo sapiens
tyrosyl-DNA phosphodiesterase I
-
 Homo sapiens

IC50 Value

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

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