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Literature summary for 5.6.2.2 extracted from

  • Ponder, J.; Yoo, B.H.; Abraham, A.D.; Li, Q.; Ashley, A.K.; Amerin, C.L.; Zhou, Q.; Reid, B.G.; Reigan, P.; Hromas, R.; Nickoloff, J.A.; LaBarbera, D.V.
    Neoamphimedine circumvents metnase-enhanced DNA topoisomerase IIalpha activity through ATP-competitive inhibition (2011), Mar. Drugs, 9, 2397-2408.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
DNA repair protein metnase enhances TopoIIalpha activity and increases resistance to TopoII? poisons Homo sapiens

Application

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

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

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
HEK-293 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

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

Synonyms Comment Organism
DNA topoisomerase IIalpha
-
Homo sapiens
topoIIalpha
-
Homo sapiens
type IIalpha DNA topoisomerase
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
39
-
-
Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP Km is 0.39 mM Homo sapiens

IC50 Value

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

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