Structural basis for catalysis and substrate specificity of a 3C-like cysteine protease from a mosquito mesonivirus.

ABSTRACT: Cavally virus (CavV) is a mosquito-borne plus-strand RNA virus in the family Mesoniviridae (order Nidovirales). We present X-ray structures for the CavV 3C-like protease (3CL^pro), as a free enzyme and in complex with a peptide aldehyde inhibitor mimicking the P4-to-P1 residues of a natural substrate. The 3CL^pro structure (refined to 1.94 Å) shows that the protein forms dimers. The monomers are comprised of N-terminal domains I and II, which adopt a chymotrypsin-like fold, and a C-terminal α-helical domain III. The catalytic Cys-His dyad is assisted by a complex network of interactions involving a water molecule that mediates polar contacts between the catalytic His and a conserved Asp located in the domain II-III junction and is suitably positioned to stabilize the de

SUBMITTER: Kanitz M 

PROVIDER: S-EPMC7111312 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature