Translational Incorporation of S-Nitrosohomocysteine into Protein

The non-protein amino acid homocysteine (Hcy), owing to its structural similarity to the protein amino acids methionine, isoleucine, and leucine, enters first steps of protein synthesis and is activated by methionyl-, isoleucyl-, and leucyl-tRNA synthetases in vivo. However, translational incorporat...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-07, Vol.275 (29), p.21813-21816
Main Author: Jakubowski, Hieronim
Format: Article
Language:English
Subjects:
Animals
Bacterial Proteins - biosynthesis
Escherichia coli
Homocysteine - analogs & derivatives
Homocysteine - metabolism
Protein Biosynthesis
Rabbits
RNA, Bacterial - metabolism
RNA, Transfer - metabolism
S-nitrosohomocysteine
tRNA
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Summary:The non-protein amino acid homocysteine (Hcy), owing to its structural similarity to the protein amino acids methionine, isoleucine, and leucine, enters first steps of protein synthesis and is activated by methionyl-, isoleucyl-, and leucyl-tRNA synthetases in vivo. However, translational incorporation of Hcy into protein is prevented by editing mechanisms of these synthetases, which convert misactivated Hcy into thiolactone. The lack of efficient interactions of the side chain of Hcy with the specificity subsite of the synthetic/editing active site is a prerequisite for editing of Hcy. Thus, if the side chain thiol of Hcy were reversibly modified with a small molecule that would enhance its binding to the specificity subsite and prevent editing, such modified Hcy is predicted to be transferred to tRNA and incorporated translationally into protein. Here I show thatS-nitroso-Hcy is in fact transferred to tRNA by methionyl-tRNA synthetase and incorporated into protein by the bacterium Escherichia coli. S-Nitroso-Hcy-tRNA also supports translation of mRNAs in a rabbit reticulocyte system. Removal of the nitroso group yields Hcy-tRNA and protein containing Hcy in peptide bonds. S-Nitrosylation-mediated translational incorporation of Hcy into protein may occur under natural conditions in cells and contribute to Hcy-induced pathogenesis in atherosclerosis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C000280200