ADP-ribose and analogues bound to the deMARylating macrodomain from the bat coronavirus HKU4.

ABSTRACT: Macrodomains are proteins that recognize and hydrolyze ADP ribose (ADPR) modifications of intracellular proteins. Macrodomains are implicated in viral genome replication and interference with host cell immune responses. They are important to the infectious cycle of Coronaviridae and Togaviridae viruses. We describe crystal structures of the conserved macrodomain from the bat coronavirus (CoV) HKU4 in complex with ligands. The structures reveal a binding cavity that accommodates ADPR and analogs via local structural changes within the pocket. Using a radioactive assay, we present evidence of mono-ADPR (MAR) hydrolase activity. In silico analysis presents further evidence on recognition of the ADPR modification for hydrolysis. Mutational analysis of residues within the binding

SUBMITTER: Hammond RG 

PROVIDER: S-EPMC7812796 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature