5v59
From Proteopedia
Crystal structure of catalytic fragment of human AlaRS in complex with Aze-SA
Structural highlights
DiseaseSYAC_HUMAN Autosomal dominant Charcot-Marie-Tooth disease type 2N. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionSYAC_HUMAN Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.[HAMAP-Rule:MF_03133] Publication Abstract from PubMedHundreds of non-proteinogenic (np) amino acids (AA) are found in plants and can in principle 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. Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid.,Song Y, Zhou H, Vo MN, Shi Y, Nawaz MH, Vargas-Rodriguez O, Diedrich JK, Yates JR, Kishi S, Musier-Forsyth K, Schimmel P Nat Commun. 2017 Dec 22;8(1):2281. doi: 10.1038/s41467-017-02201-z. PMID:29273753[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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