Low Taxol Concentration

Recovery times depend on taxol concentration as [TAX]-1/5 (see center figure).
Both GMPCPP and GTP microtubules exhibit similar behavior.
Implies the same mechanism is dictating the motion of the taxol in this regime.

Over 63% of the taxol binding sites of the microtubule are filled. Recovery times for GMPCPP bundles level off (see center figure). Implies that the few open binding sites are not affecting the motion of the taxol molecules t 1 / koff The average distance to the next open binding site ~ 7 nm.

The type of nucleotide at the E-site determines the affinity of the taxol-dimer binding reaction.

GMPCPP microtubules, with a higher binding affinity for taxol, slowed the diffusion of taxol more than GTP microtubules (see middle figure).

Thus, GMPCPP bundles always had longer recovery times than GTP bundles.

At the highest taxol concentrations,

t_GMPCPP ~ 10 t_GTP

Since t k_off^-1, this implies that

k_off^GMPCPP ~ k_off^GTP /10

Thick, dense bundles have longer recovery times than thin, sparse bundles.

Implies that taxol molecules encounter multiple microtubules as they diffuse within the bundle.

Thus, microtubule walls must be permeable to taxol.

Structural studies have shown the microtubule walls to have pores ~2nm in diameter (Meurer-Grob, et al. 2001 Biochemistry-US), and taxol is only ~1nm in diameter.