ATP synthase: the right size base model for nanomotors in nanomedicine

Abstract

Nanomedicine results from nanotechnology where molecular scale minute precise nanomotors can be used to treat disease conditions. Many such biological nanomotors are found and operate in living systems which could be used for therapeutic purposes. The question is how to build nanomachines that are compatible with living systems and can safely operate inside the body? Here we propose that it is of paramount importance to have a workable base model for the development of nanomotors in nanomedicine usage. The base model must placate not only the basic requirements of size, number, and speed but also must have the provisions of molecular modulations. Universal occurrence and catalytic site molecular modulation capabilities are of vital importance for being a perfect base model. In this review we will provide a detailed discussion on ATP synthase as one of the most suitable base models in the development of nanomotors. We will also describe how the capabilities of molecular modulation can improve catalytic and motor function of the enzyme to generate a catalytically improved and controllable ATP synthase which in turn will help in building a superior nanomotor. For comparison, several other biological nanomotors will be described as well as their applications for nanotechnology.

Figure 1

Escherichia coli  F₁F₀ ATP synthase structure: E. coli ATP synthase in the simplest form contains water soluble F₁ and membrane bound F₀ sectors. Catalytic activity ensues at the α/β interface of F₁ sector. Many inhibitors also bind to the F₁ sector which comprises five subunits (α ₃ β ₃ γδε). The proton pumping occurs at the F₀ sector comprising three subunits (ab₂c). This structure of E. coli  F₁F₀ ATP synthase is reproduced from Weber [27] with permission; copyright Elsevier.

Figure 2

Catalytic sites X-ray structure of ATP synthase depicting spatial relationship between α and β-subunit residues. The βDP site in the AlF₄ ⁻-inhibited enzyme structure is taken from [63]. E. coli residue numbering is used. It can be seen that removal of arginine from βR246 can be compensated by introduction of arginine in the neighboring residues αF291 or βN243. Dotted triangle shows the residues βLys-155, βArg-182, βArg-246, αArg-376, and αSer-347, forming a triangular Pi binding site. Figure was modified from the originally published figure in [75]. RasMol molecular visualization software was used to generate the figure.