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Based on the presumed capability of a prebiotic pocket-like entity to accommodate substrates whose stereochemistry enables the creation of chemical bonds, it is suggested that a universal symmetrical region identified within all contemporary ribosomes originated from an entity that we term the ‘proto-ribosome’. This ‘proto-ribosome’ could have evolved from an earlier machine that was capable of performing essential tasks in the RNA world, called here the ‘pre-proto-ribosome’, which was adapted for producing proteins.

In coronaviruses such as the SARS coronavirus (SARS-CoV), programmed −1 ribosomal frameshifting (−1 PRF) is used to direct the synthesis of immediate early proteins, e.g., RNA-dependent RNA polymerase (RDRP) and proteases, that are thought to prepare the infected cell for takeover by the virus. Unlike other RNA viruses which make their structural proteins first, this class of proteins is synthesized after −1 PRF, from subgenomic mRNAs produced subsequent to production of RDRP. Also unique among the coronaviruses is the inclusion of mRNA structural elements that do not appear to be essential for frameshifting. Understanding the differences between –1 PRF signals from coronaviruses and other viruses will enhance our understanding of –1 PRF in general, and will be instructive in designing new classes of antiviral therapeutics. In this chapter we summarize current knowledge and add additional insight to the function of the programmed –1 ribosomal frameshift signal present in the SARS-associated coronavirus.

Department of Chemistry, University of Kalyani, Kalyani-741 235, Nadia, West Bengal, India E-mail : nilashisnandi@yahoo.com Fax : 91-33-25828282 Manuscript received 17 February 2011, accepted 25 March 2011 Peptide synthesis is an important biological reaction. Both concerted and stepwise mechanisms are proposed for the peptide synthesis in ribosome. The stepwise mechanism takes place through a tetrahedral intermediate. We analyzed the geometry, chirality and stabilizing factors of the intermediate using a combined quantum mechanical/ semiempirical method based on a model of crystal structure. The comparison of the optimized geometry of the intermediate and transition state analog (DCSN) shows that in case of ribosomal peptide synthesis the intermediate should be tetrahedral with S-chirality. The chiral specificity of the intermediate arises from the relative position of the A-site substrate and the P-site substrate. The present computational study conclusively shows that the geometry of the carbonyl carbon atom of P-site amino acid is changed from a planer state (reactant) to another planer state (product) via a tetrahedral intermediate during the peptide bond formation in the ribosome. The tetrahedral intermediate is chiral and has S-chirality. The specificity of chiral structure of the intermediate arises from the relative position of the A-site substrate and the P-site substrate. The generation of the other isomer of the tetrahedral intermediate (R isomer) is impossible during the peptide biosynthesis in the ribosome. As the architecture of the PTC is such that P-site and A-site substrates are enclosed in specific locations, other positions of the substrates are impossible. Consequently the nucleophilic attack by the a-amino group of A-site substrate from the two faces of the carbonyl carbon atom of P-site substrate is impossible. As a result only one isomer of the tetrahedral intermediate is possible during the ribosomal peptide synthesis which is stabilized via intra as well as intermolecular hydrogen bonding interactions. The U2620 plays an important role in the stabilization of the geometry of the intermediate. This study is the first computational analysis of the structure and stabilization of the tetrahedral intermediate during the stepwise pathway of peptide synthesis.