Positional Isomers of a Non-Nucleoside Substrate Differentially Affect Myosin Function.

Molecular motors have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction of these motors is a root cause of many pathologies necessitating the need for intrinsic control over molecular motor function. Herein, we demonstrate that positional isomerism can be used as a simple and powerful tool to control the molecular motor of muscle, myosin. Using three isomers of a synthetic non-nucleoside triphosphate, we demonstrate that myosin's force- and motion-generating capacity can be dramatically altered at both the ensemble and single-molecule levels. By correlating our experimental results with computation, we show that each isomer exerts intrinsic control by affecting distinct steps in myosin's mechanochemical cycle. Our studies demonstrate that subtle variations in the structure of an abiotic energy source can be used to control the force and motility of myosin without altering myosin's structure.