Taxanes and other microtubule-stabilizing agents comprise an important class of anticancer drugs. It is well known that taxanes act by binding to beta-tubulin on the lumenal side of microtubules. However, experimental evidence obtained in recent years led to the hypothesis of an external site on the microtubule wall to which taxanes and other microtubule-stabilizing agents could bind before being internalized to their lumenal site. In the present study, different computational techniques were combined to explore the possible existence of an exposed and easily accessible binding site for microtubule-stabilizing agents on the outside of microtubules. The results obtained indicate that the conformational rearrangement of the H6-H7 hoop of beta-tubulin can form a suitable pocket on the outer microtubule surface, and that paclitaxel can efficaciously interact with this newly-proposed binding site.

Magnani, M., Maccari, G., J., A., J., D., Botta, M. (2009). Possible binding site for paclitaxelat microtubule pores. THE FEBS JOURNAL, 276, 2701-2712 [10.1111/j.1742-4658.2009.06994.x].

Possible binding site for paclitaxelat microtubule pores

MAGNANI, MATTEO;MACCARI, GIORGIO;BOTTA, MAURIZIO
2009-01-01

Abstract

Taxanes and other microtubule-stabilizing agents comprise an important class of anticancer drugs. It is well known that taxanes act by binding to beta-tubulin on the lumenal side of microtubules. However, experimental evidence obtained in recent years led to the hypothesis of an external site on the microtubule wall to which taxanes and other microtubule-stabilizing agents could bind before being internalized to their lumenal site. In the present study, different computational techniques were combined to explore the possible existence of an exposed and easily accessible binding site for microtubule-stabilizing agents on the outside of microtubules. The results obtained indicate that the conformational rearrangement of the H6-H7 hoop of beta-tubulin can form a suitable pocket on the outer microtubule surface, and that paclitaxel can efficaciously interact with this newly-proposed binding site.
2009
Magnani, M., Maccari, G., J., A., J., D., Botta, M. (2009). Possible binding site for paclitaxelat microtubule pores. THE FEBS JOURNAL, 276, 2701-2712 [10.1111/j.1742-4658.2009.06994.x].
File in questo prodotto:
File Dimensione Formato  
j.1742-4658.2009.06994.x.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 779.17 kB
Formato Adobe PDF
779.17 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/20965
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo