4 - The bottle neck: macromolecular sequences

Summary

Introduction

Having highlighted some of the data and issues about the prebiotic chemistry of low-molecular-weight compounds, let's now turn to the functional long chains – mostly proteins and nucleic acids. The first part of this chapter is devoted to the prebiotic chemistry of biopolymers, the second part, which will necessarily be more speculative, to ideas of conceiving the very origin of macromolecular sequences.

Our biology is regulated by the catalytic power of enzymes and by the encoding power of nucleic acids. This chapter may begin with one very general question: “Why macromolecules? What is so peculiar in their great length that makes these molecules essential for life? Why didn't nature do it all using smaller peptides or smaller oligonucleotides? Why this … and not that?”

The question “why are enzymes macromolecules?” is an old issue in structural biochemistry, and one with which I liked to play around in my younger days (Luisi, 1979). Clearly, there are good reasons for long chains: only a long chain permits the dilution in the same string of many active residues and, simultaneously, their mutual proximity due to the forced folding; in turn, this folding and the corresponding conformational rigidity is due to the very large number of intramolecular interactions, which is only possible in long chains; the consequence of the length is an elaborate three-dimensional architecture that brings forth a particular micro-environment and reactivity of the active site; the large size is also responsible for the overall physicochemical properties, such as solubility in water or affinity to the membrane, conformational changes and cooperativity.