3p06

Publication Abstract from PubMed

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 A resolution. The structure reveals how the enzyme can recognize its own carboxy-terminus during the VP4/VP3 cleavage event. The methyl sidechains 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 Ogamma 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 (IPNV) VP4 explains the narrower specificity observed in the cleavage sites of TV-1 VP4.

Crystal structure of a viral protease intramolecular acyl-enzyme complex. Insights into cis-cleavage at the VP4/VP3 junction of Tellina birnavirus.,Chung IY, Paetzel M J Biol Chem. 2011 Feb 2. PMID:21288899^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.