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Life 2017, 7(1), 6; doi:10.3390/life7010006

Homocysteine Editing, Thioester Chemistry, Coenzyme A, and the Origin of Coded Peptide Synthesis †

1
Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA
2
Department of Biochemistry and Biotechnology, University of Life Sciences, Poznan 60-632, Poland
Academic Editor: Koji Tamura
Received: 3 January 2017 / Revised: 26 January 2017 / Accepted: 3 February 2017 / Published: 9 February 2017
View Full-Text   |   Download PDF [7232 KB, uploaded 16 February 2017]   |  

Abstract

Aminoacyl-tRNA synthetases (AARSs) have evolved “quality control” mechanisms which prevent tRNA aminoacylation with non-protein amino acids, such as homocysteine, homoserine, and ornithine, and thus their access to the Genetic Code. Of the ten AARSs that possess editing function, five edit homocysteine: Class I MetRS, ValRS, IleRS, LeuRS, and Class II LysRS. Studies of their editing function reveal that catalytic modules of these AARSs have a thiol-binding site that confers the ability to catalyze the aminoacylation of coenzyme A, pantetheine, and other thiols. Other AARSs also catalyze aminoacyl-thioester synthesis. Amino acid selectivity of AARSs in the aminoacyl thioesters formation reaction is relaxed, characteristic of primitive amino acid activation systems that may have originated in the Thioester World. With homocysteine and cysteine as thiol substrates, AARSs support peptide bond synthesis. Evolutionary origin of these activities is revealed by genomic comparisons, which show that AARSs are structurally related to proteins involved in coenzyme A/sulfur metabolism and non-coded peptide bond synthesis. These findings suggest that the extant AARSs descended from ancestral forms that were involved in non-coded Thioester-dependent peptide synthesis, functionally similar to the present-day non-ribosomal peptide synthetases. View Full-Text
Keywords: aminoacyl-tRNA synthetase; homocysteine editing; thioester; coenzyme A; non-coded peptide synthesis; prebiotic chemistry; thioester world; evolution aminoacyl-tRNA synthetase; homocysteine editing; thioester; coenzyme A; non-coded peptide synthesis; prebiotic chemistry; thioester world; evolution
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Jakubowski, H. Homocysteine Editing, Thioester Chemistry, Coenzyme A, and the Origin of Coded Peptide Synthesis †. Life 2017, 7, 6.

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