5LAK

Ligand-bound structure of Cavally Virus 3CL Protease

Summary for 5LAK

• Entry DOI: 10.2210/pdb5lak/pdb
• Related: 5LAC
• Descriptor: 3Cl Protease, BEZ-TYR-TYR-ASN-ECC Peptide inhibitor, PENTAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: protease, mesonivirus, 3cl, peptide-bound, hydrolase
• Biological source: Cavally virus; More
• Total number of polymer chains: 7
• Total formula weight: 145746.16

Authors

Kanitz, M.,Heine, A.,Diederich, W.E. (deposition date: 2016-06-14, release date: 2017-07-12, Last modification date: 2024-01-10)

Primary citation

Kanitz, M.,Blanck, S.,Heine, A.,Gulyaeva, A.A.,Gorbalenya, A.E.,Ziebuhr, J.,Diederich, W.E.
Structural basis for catalysis and substrate specificity of a 3C-like cysteine protease from a mosquito mesonivirus.
Virology, 533:21-33, 2019

PubMed 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), as a free enzyme and in complex with a peptide aldehyde inhibitor mimicking the P4-to-P1 residues of a natural substrate. The 3CL 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 developing positive charge of the catalytic His in the transition state during catalysis. The study also reveals the structural basis for the distinct P2 Asn-specific substrate-binding pocket of mesonivirus 3CLs.

PubMed: 31078932
DOI: 10.1016/j.virol.2019.05.001

Experimental method

X-RAY DIFFRACTION (2.299 Å)