Naslov
Crosstalk of the synthetic and editing pathways that excludes artificial amino acids from translation

Autori
Gruić-Sovulj, I

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of abstracts, IUBMB Focused Meeting on the Aminoacyl-tRNA synthetases / Alexander, Rebecca ; Francklyn, Christopher ; Roy, Herve - Lahti, 2017, 74-74

Skup
IUBMB Focused Meeting on the Aminoacyl-tRNA synthetases

Mjesto i datum
Clearwater (FL), Sjedinjene Američke Države, 29.10.2017. - 02.11.2017

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
mistranslation, artifical amino acids, aminoacyl-tRNA synthetases, editing

Sažetak
Fluorinated amino acids are attractive synthetic compounds that may be used as protein building blocks for tailoring novel properties of peptides and proteins. Given the lack of evolutionary pressure against unnatural compounds, it had been assumed that translational quality control would not obstruct their use in protein synthesis. Unexpectedly, we have demonstrated that participation of trifluorethylglycine (TfeGly) in translation is efficiently hindered by the post- transfer editing activity of isoleucyl-tRNA synthetase (IleRS) [1]. A remarkable finding is that the observed editing against TfeGly-tRNAIle is reduced to the level displayed by IleRS against its cognate product Ile-tRNAIle. Using editing domain variants of IleRS and various kinetic approaches we have obtained clear evidence that the slow hydrolytic step is kinetically competent in the wild-type enzyme because dissociation of TfeGly-tRNAIle is significantly perturbed. This finding suggests that kinetic partitioning of tRNAs may significantly differ depending on whether they are aminoacylated with artificial or standard amino acids, presumably as a consequence of the peculiar interactions that may be established between the enzyme and the non-natural substrates. Idiosyncrasies of fluorinated amino acids participating in aminoacylation and editing will be discussed. References: 1. Völler JS, Dulic M, Gerling-Driessen UI, Biava H, Baumann T, Budisa N*, Gruic-Sovulj I*, Koksch B*. Discovery and Investigation of Natural Editing Function against Artificial Amino Acids in Protein Translation ACS Cent Sci. 2017 3(1):73-80.

Izvorni jezik
Engleski

POVEZANOST RADA