Abstract
The chiral-selective aminoacylation of an RNA minihelix is a potential progenitor to modern tRNA-based protein synthesis using l-amino acids. This article describes the molecular basis for this chiral selection. The extended double helical form of an RNA minihelix with a CCA triplet (acceptor of an amino acid), an aminoacyl phosphate donor nucleotide (mimic of aminoacyl-AMP), and a bridging nucleotide facilitates chiral-selective aminoacylation. Energetically, the reaction is characterized by a downhill reaction wherein an amino acid migrates from a high-energy acyl phosphate linkage to a lower-energy carboxyl ester linkage. The reaction occurs under the restriction that the nucleophilic attack of O, from 3′-OH in the terminal CCA, to C, from C=O in the acyl phosphate linkage, must occur at a Bürgi-Dunitz angle, which is defined as the O–C=O angle of approximately 105°. The extended double helical form results in a steric hindrance at the side chain of the amino acid leading to chiral preference combined with cation coordinations in the amino acid and the phosphate oxygen. Such a system could have developed into the protein biosynthetic system with an exclusively chiral component (l-amino acids) via (proto) ribosomes.
Highlights
A distinguishing characteristic of the biological system is that the building blocks are composed exclusively of homochiral molecules
New roles of non-coding RNA have recently been discovered [3,4,5], the most well-known and primary function of RNA is to mediate the genetic information encoded in DNA in the central dogma: mRNAs are transcribed from DNA, after which amino acids are incorporated into proteins on ribosomes via aminoacyl-tRNAs, according to the nucleotide sequences found on the mRNAs [6,7]
In the current biological system, tRNA aminoacylation is the step where RNA and amino acids interact with each other; the correspondence between RNA codons and amino acids is known as the genetic code [14]
Summary
A distinguishing characteristic of the biological system is that the building blocks are composed exclusively of homochiral molecules. The non-enzymatic aminoacylation system is composed of 3 molecules: an RNA minihelix (amino acid acceptor), an aminoacyl phosphate nucleotide (amino acid donor), and a bridging nucleotide. These molecules constitute an extended double-helix structure, and all of the base pairings hybridizing each chain are of the Watson-Crick type. TRNAs charged with L-amino acids could form proteins composed of L-amino acids by using proto-ribosomes much the same as modern proteins In this context, the chiral-selective aminoacylation of RNA is a crucial development in consideration of the origin of amino acid homochirality in biological systems [19]. The putative evolutionary story is described in detail in the literature [25,26,27,28], and here, I would like to focus on the molecular mechanism determining the chiral selectivity of the reaction
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