3P06

Crystal structure of Tellina virus 1 VP4 protease in the form of an intra-molecular(cis)acyl-enzyme complex.

Summary for 3P06

• Entry DOI: 10.2210/pdb3p06/pdb
• Related: 2GEF 2PNL 2PNM
• Descriptor: VP4 protein, SULFATE ION, GLYCEROL, ... (7 entities in total)
• Functional Keywords: cis-cleavage, intramolecular acyl-enzyme, ester-linkage, alpha/beta protein, protease, polyprotein processing, acyl-enzyme, hydrolase
• Biological source: Tellina virus 1
• Total number of polymer chains: 1
• Total formula weight: 21109.87

Authors

Chung, I.Y.W.,Paetzel, M. (deposition date: 2010-09-27, release date: 2011-02-02, Last modification date: 2011-07-13)

Primary citation

Chung, I.Y.,Paetzel, M.
Crystal Structure of a Viral Protease Intramolecular Acyl-enzyme Complex: INSIGHTS INTO cis-CLEAVAGE AT THE VP4/VP3 JUNCTION OF TELLINA BIRNAVIRUS.
J.Biol.Chem., 286:12475-12482, 2011

PubMed Abstract: Viruses of the Birnaviridae family are characterized by their bisegmented double-stranded RNA genome that resides within a single-shelled non-enveloped icosahedral particle. They infect birds, aquatic organisms, and insects. Tellina virus 1 (TV-1) is an Aquabirnavirus isolated from the mollusk Tellina tenuis. It encodes a polyprotein (NH2-pVP2-X-VP4-VP3-COOH) that is cleaved by the self-encoded protease VP4 to yield capsid precursor protein pVP2, peptide X, and ribonucleoprotein VP3. Here we report the crystal structure of an intramolecular (cis) acyl-enzyme complex of TV-1 VP4 at 2.1-Å resolution. The structure reveals how the enzyme can recognize its own carboxyl terminus during the VP4/VP3 cleavage event. The methyl side chains of Ala830(P1) and Ala828(P3) at the VP4/VP3 junction point into complementary shallow and hydrophobic S1 and S3 binding pockets adjacent to the VP4 catalytic residues: nucleophile Ser738 and general base Lys777. The electron density clearly shows that the carbonyl carbon of Ala830 is covalently attached via an ester bond to the Oγ of Ser738. A highly ordered water molecule in the active site is coordinated in the proper position to act as the deacylating water. A comparative analysis of this intramolecular (cis) acyl-enzyme structure with the previously solved intermolecular (trans) acyl-enzyme structure of infectious pancreatic necrosis virus VP4 explains the narrower specificity observed in the cleavage sites of TV-1 VP4.

PubMed: 21288899
DOI: 10.1074/jbc.M110.198812

Experimental method

X-RAY DIFFRACTION (2.1 Å)