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

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Abstract
The crystal structure of the 2A proteinase from human rhinovirus serotype 2 (HRV2‐2Apro) has been solved to 1.95 Å resolution. The structure has an unusual, although chymotrypsin‐related, fold comprising a unique four‐stranded β sheet as the N‐terminal domain and a six‐stranded β barrel as the C‐terminal domain. A tightly bound zinc ion, essential for the stability of HRV2‐2Apro, is tetrahedrally coordinated by three cysteine sulfurs and one histidine nitrogen. The active site consists of a catalytic triad formed by His18, Asp35 and Cys106. Asp35 is additionally involved in an extensive hydrogen‐bonding network. Modelling studies reveal a substrate‐induced fit that explains the specificity of the subsites S4, S2, S1 and S1′. The structure of HRV2‐2Apro suggests the mechanism of the cis cleavage and its release from the polyprotein.