title: Aminoacylation of coenzyme A and pantetheine by aminoacyl-tRNA synthetases: possible link between noncoded and coded peptide synthesis.
abstract: Isoleucyl-tRNA synthetase (IleRS) catalyzes transfer of isoleucine from the enzyme-bound Ile-AMP and Ile-tRNA to the thiol group of coenzyme A, forming a thioester, Ile-S-CoA. Identity of Ile-S-CoA has been confirmed by several enzymatic and chemical tests. The synthesis of Ile-S-CoA, like the synthesis of other isoleucyl thioesters, is strongly shifted toward products. Other aminoacyl-tRNA synthetases, such as MetRS, AspRS, and SerRS also use CoA-SH as an acceptor for their cognate amino acids. Pantetheine also serves as an amino acid acceptor in reactions catalyzed by AspRS, IleRS, and MetRS, forming corresponding aminoacyl-S-pantetheine thioesters. It appears that CoA-SH reacts with activated amino acids by binding to each synthetase at a site, separate from the tRNA and ATP binding sites, that includes the thiol-binding subsite. These and other data support a hypothesis that the present-day aminoacyl-tRNA synthetases have originated from ancestral forms that were involved in noncoded thioester-dependent peptide synthesis, functionally similar to the present-day nonribosomal peptide synthesis by multi-enzyme thiotemplate systems.
authors.affiliation: Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103, USA. jakubows@umdnj.edu
authors.forename: H
authors.initials: H
authors.lastname: Jakubowski
mesh_terms: D000215:Acylation; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D003065:Coenzyme A / Q000378:metabolism*; D019143:Evolution, Molecular; D007533:Isoleucine-tRNA Ligase / Q000378:metabolism*; D010204:Pantetheine / Q000378:metabolism*; D010452:Peptide Biosynthesis; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D012346:RNA, Transfer, Amino Acyl; D010204:Pantetheine; D000604:Amino Acyl-tRNA Synthetases; D007533:Isoleucine-tRNA Ligase; D003065:Coenzyme A