Chiral-selective aminoacylation of an RNA minihelix: Mechanistic features and chiral suppression

Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13750-2. doi: 10.1073/pnas.0606070103. Epub 2006 Sep 1.

Abstract

Aminoacylation of RNA minihelices is speculated to be a key step in the transition from the putative RNA world to the theater of proteins. This reaction affords the opportunity to make chiral selection of an l- or d-amino acid and thus determine the ultimate chirality that is incorporated into proteins. Previous work showed chiral preference of aminoacylation with a nonprotein, nonribozyme, RNA-directed aminoacylation system. This preference was, in turn, determined by the preexisting chirality of the RNA. The alpha-amino group attached to the asymmetric alpha-carbon of the amino acid was an obvious candidate to play a role in chiral selectivity through interactions with the RNA. Also not clear was whether a simple manipulation could change the chiral selectivity, thereby giving insight into the basis of chiral selection in the first place. Here we show, surprisingly, no role for the free alpha-amino group in chiral selection. However, by a sequence manipulation, chiral preference was suppressed and partly reversed. This result and those with further RNA constructs support the idea that the chiral preference for an l-amino acid in these constructs depends on avoiding a sugar-pucker-sensitive steric clash between a pendant group of a base with the amino acid side chain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Base Sequence
  • Carbohydrates / chemistry
  • Nucleic Acid Conformation
  • RNA / chemistry*
  • Stereoisomerism
  • Transfer RNA Aminoacylation*

Substances

  • Amino Acids
  • Carbohydrates
  • RNA