Mn <sup>2+</sup> coordinates Cap-0-RNA to align substrates for efficient 2′- <i>O</i> -methyl transfer by SARS-CoV-2 nsp16
G. Minasov, Mónica Rosas‐Lemus, L. Shuvalova, Nicole L. Inniss, J.S. Brunzelle, Courtney M. Daczkowski, Paul Hoover, Andrew D. Mesecar, K.J.F. Satchell
Abstract
-methyltransferases with capped RNAs from different organisms revealed that the four-residue insert unique to coronavirus nsp16 alters the backbone conformation of the capped RNA in the binding groove, thereby promoting catalysis. This insert is highly conserved across coronaviruses, and its absence in mammalian methyltransferases makes this region a promising site for structure-guided drug design of selective coronavirus inhibitors.
Topics & Concepts
RNAMethyltransferaseSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)ChemistryCoronavirus disease 2019 (COVID-19)Residue (chemistry)PhysicsBiochemistryDNAMethylationMedicineGeneDiseasePathologyInfectious disease (medical specialty)RNA modifications and cancerRNA and protein synthesis mechanismsBacteriophages and microbial interactions