LAUSR

Significance Kinesin, an amazing biological machine, converts chemical energy from the ATP hydrolysis into mechanical energy to perform different cellular activities. Several single-point gene-level mutations in the neuronal kinesin motor (KIF5A) are linked to a neurodegenerative disease, hereditary spastic paraplegia (HSP). Earlier we demonstrated that some of the mutations produce inefficient kinesins that can only walk a few steps on a microtubule as opposed to several hundred by normal kinesin. Here, a different mutation is studied that produces very sluggish kinesin by reducing the rate of hydrolysis of ATP. This asparagine-to-serine mutation at distal location to the active site is shown to disrupt pre-organization environment required for efficient ATP hydrolysis reaction in kinesin through a second sphere effect.