Principles of chemical geometry underlying chiral selectivity in RNA minihelix aminoacylation
Tadashi Ando Shunichi Takahashi Koji Tamura
Nucleic Acids Research, Volume 46, Issue 21, 30 November 2018, Pages 11144–11152, https://doi.org/10.1093/nar/gky909
Published: 15 October 2018
Article history
Received: 08 August 2018 Revision Received: 10 September 2018
Accepted: 02 October 2018
Source/Fonte: Courses Lumen Learning
Abstract
The origin of homochirality in L-amino acid in proteins is one of the mysteries of the evolution of life. Experimental studies show that a non-enzymatic aminoacylation reaction of an RNA minihelix has a preference for L-amino acid over D-amino acid. The reaction initiates by approaching of a 3′-oxygen of the RNA minihelix to the carbonyl carbon of an aminoacyl phosphate oligonucleotide. Here, employing molecular dynamics simulations, we examined the possible mechanisms that determine this chiral selectivity. The simulation system adopted a geometry required for the chemical reaction to occur more frequently with L-alanine than that with D-alanine. For L-alanine, the structure with this geometry was formed by a combination of stable dihedral angles along alanyl phosphate backbone with a canonical RNA structure, where the methyl group of alanine was placed on the opposite side of the approaching 3′-hydroxyl group with respect to the carbonyl plane. For D-alanine, the methyl group and the 3′-hydroxyl group were placed on the same side with respect to the carbonyl plane, which significantly decreased its ability to approach 3′-oxygen close to the carbonyl carbon compared to L-alanine. The mechanism suggested herein can explain experimentally observed chiral preferences.
Issue Section: Chemical Biology and Nucleic Acid Chemistry
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