The kinetic mechanism of kinesin

The chemical kinetic mechanism of kinesin (K) is considered by using a consensus scheme incorporating biochemically defined open, closed and trapped states. In the absence of microtubules, the dominant species is a trapped K(.)ADP state, which is defined by its ultra-slow release of ADP (off rate, k(off) 0.002 s(-1)) and weak microtubule binding (dissociation constant, K-d 10-20 muM). Once bound, this trapped state equilibrates with a strongly binding open state that rapidly releases ADP (k(off) approximate to 300 s(-1)). After ADP release, Mg(.)ATP binds (on rate, k(on) approximate to 2 muM(-1) s(-1)) driving formation of a closed state that is defined by hydrolysis competence and by strong binding to microtubules. Hydrolysis (k(hyd) approximate to 100-300 s(-1)) and phosphate release (k(off) > 100 s(-1)) both occur in this microtubule-bound closed state. Phosphate release acts as a gate that controls reversion to the trapped K(.)ADP state, which detaches from the microtubule, completing the cycle.