Foot-and-mouth disease virus leader proteinase: a papain-like enzyme requiring an acidic environment in the active site

Abstract

Foot-and-mouth disease virus leader proteinase (L pro), a papain-like cysteine proteinase, has six acidic amino acids between 4 Å and 11 Å of the catalytic dyad of Cys51 and His148. In contrast, in papain and related enzymes, only one acidic residue lies within this distance. We have examined by site-directed mutagenesis the importance of each of these residues for L pro self-processing and cleavage of its cellular substrate, eukaryotic initiation factor 4GI. Only substitution of the electrostatic charge of aspartate 164 affected enzyme activity. Thus, in contrast to the prototype papain, L pro activity requires a negative charge 4.5 Å from the catalytic dyad.