The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis

The crystal structure of the 2A proteinase from human rhinovirus serotype 2 (HRV2-2A(pro)) has been solved to 1.95 Angstrom resolution. The structure has an unusual, although chymotrypsin-related, fold comprising a unique fou r-stranded beta sheet as the N-terminal domain and a six-stranded beta barr el as the C-terminal domain, A tightly bound zinc ion, essential for the st ability of HRV2-2A(pro), is tetrahedrally coordinated by three cysteine sul furs and one histidine nitrogen. The active site consists of a catalytic tr iad formed by His18, Asp35 and Cys106 Asp35 is additionally involved in an extensive hydrogen-bonding network, Modelling studies reveal a substrate-in duced fit that explains the specificity of the subsites S4, S2, S1 and S1', The structure of HRV2-2A(pro) suggests the mechanism of the cis cleavage a nd its release from the polyprotein.