Reflections on the Origin of Coded Protein Biosynthesis

TL;DR

The paper explores how early life may have used simple chemical features to catalyze protein synthesis, which could explain the origins of coded biosynthesis.

Contribution

It highlights the role of substrate-assisted catalysis and entropy traps in primordial biocatalytic mechanisms.

Findings

Substrate-assisted catalysis and entropy traps simplify reactions in primordial biocatalysts.

β-d-ribose and phosphate were likely selected for early coding polymers due to their reactivity.

Modern enzymes differ mechanistically from these simpler primordial catalysts.

Abstract

The principle of continuity posits that some central features of primordial biocatalytic mechanisms should still be present in the genetically dependent pathway of protein synthesis, a crucial step in the emergence of life. Key bimolecular reactions of this process are catalyzed by DNA-dependent RNA polymerases, aminoacyl-tRNA synthetases, and ribosomes. Remarkably, none of these biocatalysts contribute chemically active groups to their respective reactions. Instead, structural and functional studies have demonstrated that nucleotidic α-phosphate and β-d-ribosyl 2′ OH and 3′ OH groups can help their own catalysis, a process which, consequently, has been called “substrate-assisted”. Furthermore, upon binding, the substrates significantly lower the entropy of activation, exclude water from these catalysts’ active sites, and are readily positioned for a reaction. This binding mode has been described as an “entropy trap”. The combination of this effect with substrate-assisted catalysis results in reactions that are stereochemically and mechanistically simpler than the ones found in most modern enzymes. This observation is consistent with the way in which primordial catalysts could have operated; it may also explain why, thanks to their complementary reactivities, β-d-ribose and phosphate were naturally selected to be the central components of early coding polymers.

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