Fiche publication
Date publication
octobre 2024
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GRANDEMANGE Stéphanie
Tous les auteurs :
D'Anna L, Froux A, Rainot A, Spinello A, Perricone U, Barbault F, Grandemange S, Barone G, Terenzi A, Monari A
Lien Pubmed
Résumé
The presence of a guanine quadruplex in the opening reading frame of the messenger RNA coding for the transmembrane serine protease 2 (TMPRSS2) may pave the way to original anticancer and host-oriented antiviral strategy. Indeed, TMPRSS2 in addition to being overexpressed in different cancer types, is also related to the infection of respiratory viruses, including SARS-CoV-2, by promoting the cellular and viral membrane fusion through its proteolytic activity. The design of selective ligands targeting TMPRSS2 messenger RNA requires a detailed knowledge, at atomic level, of its structure. Therefore, we have used an original experimental-computational protocol to predict the first resolved structure of the parallel guanine quadruplex secondary structure in the RNA of TMPRSS2, which shows a rigid core flanked by a flexible loop. This represents the first atomic scale structure of the guanine quadruplex structure present in TMPRSS2 messenger RNA.
Mots clés
Electronic Circular Dichroism, Guanine Quadruplexex, Messenger RNA, QM/MM Methods, molecular dynamics
Référence
Chemistry. 2024 10 4;:e202403572
