2Myosin Motors: The Chemical Restraints Imposed by ATP

Most molecular motors use ATP. This is not surprising since this is the univer-sal currency of energy for most of life’s processes. The question to be addressed in this chapter is how does the fundamental chemistry of ATP hydrolysis in-fluence the observed organization of linear molecular motors seen today with a focus on myosin. This chapter is written to ask in simple terms what can be gained by reconsidering the chemistry of ATP hydrolysis. 2.1 Chemistry and Thermodynamics of ATP Hydrolysis Adenosine triphosphate is a simple molecule whose hydrolysis to either ADP and inorganic phosphate or AMP and pyrophosphate is used to drive many otherwise thermodynamically unfavorable reactions. Its value arises from the large exergonic free energy associated with these hydrolysis reactions (∆G ◦ ′ = −32.2 and −30.5 kJ ·mol−1 respectively [1]). Compounds such as ATP are often referred to as “high energy ” intermediates, which is a qualita-tively convenient way of accounting for its role in biological processes. How-ever, such terminology is inadequate for explaining the molecular basis for its exergonic properties, or more importantly, accounting for the chemical and atomic details that are seen in the enzymes that use this substrate. From the chemical perspective the phosphoester bond joining the β and γ phosphoryl groups is no different from any other single phosphorous oxy-gen linkage, so that the high energy is not associated with the linkage itself. Indeed, ATP is a surprisingly stable molecule in aqueous solution, which con-tributes to its value as a participant in biological transformations. The source of the large free energy of hydrolysis arises from differences in electronic and electrostatic properties of the reactants and products. One source of the fre