6533b81ffe1ef96bd1277781
RESEARCH PRODUCT
Investigating the inhibition of FTSJ1 a tryptophan tRNA-specific 2’-O-methyltransferase by NV TRIDs, as a mechanism of readthrough in nonsense mutated CFTR
Pietro Salvatore CarolloMarco TutoneGiulia CullettaIgnazio FiducciaFederica CorraoIvana PibiriMaria Grazia ZizzoRaffaella MelfiAndrea PaceAnna Maria AlmericoLaura Lentinisubject
Settore BIO/18 - GeneticaKeywords: FTSJ1 methyltransferase tRNA readthrough stop codon mutation small molecules docking molecular dynamics MM-GBSASettore CHIM/06 - Chimica OrganicaSettore CHIM/08 - Chimica Farmaceuticadescription
Abstract: Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations, which generate a Premature Termination Codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ri-bosome’s capacity to skip a PTC, thus generating a full-length protein. “TRIDs” are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We in-vestigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their readthrough activity by in silico analysis and in vitro studies. Our results suggest a likely inhibition of FTSJ1, a tryptophan tRNA-specific 2’-O-methyltransferase.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2023-06-01 |