Unraveling the cGAS catalytic mechanism upon DNA activation through molecular dynamics simulations

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Soler, J (Author) Other; Paiva, P (Author) Other; Ramos, MJ (Author) Other; Pedro A Fernandes (Author) FCUP; Brut, M (Author) Other

Journal

Title: Physical Chemistry Chemical Physics

Vol. 23

Pages: 9524-9531

ISSN: 1463-9076

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00T-V8V

DOI: 10.1039/d1cp00378j

Abstract (EN): Cyclic GMP-AMP Synthase (cGAS) is activated upon DNA binding and catalyzes the synthesis of 2 ',3 '-cGAMP from GTP and ATP. This cyclic dinucleotide is a messenger that triggers the autoimmune system of eukaryotic cells. In this study, we propose a Molecular Dynamics (MD) investigation of cGAS activation. We notably provide insights into the motion of the activation loop, both from a mechanical point of view and considering its role in the catalysis of cGAMP production. We finally shed light on the reaction resulting in cGAMP synthesis. Two possible catalytic routes (referred to as GTP-ATP and ATP-GTP) are proposed based on the active site occupancy, paving the way toward further exploration of the reaction mechanism.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8