Details

Autor(en) / Beteiligte

• Luo, Lusong
• Carson, Jeffrey D
• Dhanak, Dashyant
• Jackson, Jeffrey R
• Huang, Pearl S
• Lee, Yan
• Sakowicz, Roman
• Copeland, Robert A

Titel

Mechanism of Inhibition of Human KSP by Monastrol:  Insights from Kinetic Analysis and the Effect of Ionic Strength on KSP Inhibition

Ist Teil von

• Biochemistry (Easton), 2004-12, Vol.43 (48), p.15258-15266

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• Kinesin motor proteins utilize the energy from ATP hydrolysis to transport cellular cargo along microtubules. Kinesins that play essential roles in the mechanics of mitosis are attractive targets for novel antimitotic cancer therapies. Monastrol, a cell-permeable inhibitor that specifically inhibits the kinesin Eg5, the Xenopus laevis homologue of human KSP, can cause mitotic arrest and monopolar spindle formation. In this study, we show that the extent of monastrol inhibition of KSP microtubule-stimulated ATP hydrolysis is highly dependent upon ionic strength. Detailed kinetic analysis of KSP inhibition by monastrol in the presence and absence of microtubules suggests that monastrol binds to the KSP−ADP complex, forming a KSP−ADP−monastrol ternary complex, which cannot bind to microtubules productively and cannot undergo further ATP-driven conformational changes.