Activating Compound | Comment | Organism | Structure |
---|---|---|---|
DNA repair protein metnase | enhances TopoIIalpha activity and increases resistance to TopoII? poisons | Homo sapiens |
Application | Comment | Organism |
---|---|---|
drug development | type IIalpha DNA topoisomerase is among the most important clinical drug targets for the treatment of cancer | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
doxorubicin | - |
Homo sapiens | |
etoposide | - |
Homo sapiens | |
ICRF-193 | a TopoIIalpha inhibitor that binds allosterically in proximity to the N-terminal ATPase site, DNA repair protein metnase increases resistance of the enzyme to ICRF-193 | Homo sapiens | |
additional information | another marine alkaloids from Xestospongia sp., amphimedine, is biologically inactive as an antitumor agent | Homo sapiens | |
neoamphimedine | a marine alkaloid from Xestospongia sp., potently inhibits TopoIIalpha-dependent DNA decatenation in the presence of Metnase , circumvents DNA repair protein metnase-enhanced DNA topoisomerase IIalpha activity through ATP-competitive inhibition by binding ata the N-terminal ATPase sites of TopoIIalpha, key interactions observed with neoamphimedine are a network of hydrogen bonds with Ser148, Ser149, and Asn150, and with Asn91 through an ordered water molecule , molecular modeling, oveview | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HEK-293 cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | TopoIIalpha-mediated catenation of plasmid DNA and kinetoplast DNA comprising small interlocked supercoiled circular DNA | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
DNA topoisomerase IIalpha | - |
Homo sapiens |
topoIIalpha | - |
Homo sapiens |
type IIalpha DNA topoisomerase | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
39 | - |
- |
Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
- |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | Km is 0.39 mM | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0005 | - |
inhibition of DNA catenation, pH 8.0, 39°C | Homo sapiens | neoamphimedine | |
0.002 | - |
inhibition of ATPase activity, pH 8.0, 39°C | Homo sapiens | neoamphimedine |
General Information | Comment | Organism |
---|---|---|
physiological function | the enzyme plays a critical role in cell cycle progression by relieving various types of topological strain induced in DNA double strands during replication, transcription, and chromosome segregation | Homo sapiens |