Double mimicry evades tRNA synthetase editing by
toxic vegetable-sourced non-proteinogenic amino
, Huihao Zhou
, My-Nuong Vo
, Yi Shi
, Mir Hussain Nawaz
, Oscar Vargas-Rodriguez
Jolene K. Diedrich
, John R. Yates III
, Shuji Kishi
, Karin Musier-Forsyth
& Paul Schimmel
Hundreds of non-proteinogenic (np) amino acids (AA) are found in plants and can in prin-
ciple enter human protein synthesis through foods. While aminoacyl-tRNA synthetase
(AARS) editing potentially provides a mechanism to reject np AAs, some have pathological
associations. Co-crystal structures show that vegetable-sourced azetidine-2-carboxylic acid
(Aze), a dual mimic of proline and alanine, is activated by both human prolyl- and alanyl-
tRNA synthetases. However, it inserts into proteins as proline, with toxic consequences
in vivo. Thus, dual mimicry increases odds for mistranslation through evasion of one but not
both tRNA synthetase editing systems.
Corrected: Author correction
The Scripps Laboratories for tRNA Synthetase Research and the Department of Molecular Medicine, The Skaggs Institute for Chemical Biology, The Scripps
Research Institute, 92037 La Jolla, CA, USA.
Department of Chemistry and Biochemistry, Center for RNA Biology, The Ohio State University, Columbus, OH
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
The Scripps Laboratories for tRNA Synthetase
Research and Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA.
Present address: Research Center for Drug
Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, 510006 Guangzhou, China.
Present address: Department of Chemistry, New York
University, Abu Dhabi, PO Box 129188, United Arab Emirates. Correspondence and requests for materials should be addressed to
P.S. (email: firstname.lastname@example.org)