Variable Macro X Domain of SARS-CoV-2 Retains the Ability to Bind ADP-ribose

David N. Frick; Rajdeep S. Virdi; Nemanja Vuksanovic; Narayan Dahal; Nicholas R Silvaggi

The tertiary structure, as expected, ranges from nearly identical to very similar to those of other coronavirus macro domains, including: SARS CoV-1 (2FAV 9 ; 74.7% sequence identity) with a root mean square deviation (RMSD) value for 162 of 172 Cα atoms of 0.6 Å; MERS CoV (5DUS 8 ; 42.2% identical) with a 1.2 Å RMSD for 161 of 172 Cα atoms; human alpha coronavirus 229E (3EWR 10 ; 32.5% identical) with a 1.5 Å RMSD for 154 of 172 Cα atoms; feline coronavirus (FCoV; 3JZT 11 26.8% identical) with a 1.5 Å RMSD for 153 of 172 Cα atoms; and the gamma CoV infectious bronchitis virus (IBV; 3EWP 10 26.7% identical) with a 2.1 Å RMSD for 150 of 172 Cα atoms. The regions of high sequence conservation are not clustered in any particular region(s) of the molecule (Fig. 4B ). This makes sense in light of the fact that the protein atoms involved in hydrogen bonding interactions with the ligands in these structures are more often part of the main chain; there are relatively few interactions of side chains with the ligands.