Foot-and-mouth disease virus leader proteinase: a papain-like enzyme requiring an acidic environment in the active site.
Foot-and-mouth disease virus leader proteinase (L(pro)), a papain-like cysteine proteinase, has six acidic amino acids between 4 A and 11 A 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 A from the catalytic dyad.
Kronovetr
Jakub
J
Institute for Medical Biochemistry, Division of Biochemistry, University of Vienna, Dr. Bohr-Gasse 9/3, Austria.
Skern
Tim
T
D000600:Amino Acids, Dicarboxylic / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D020134:Catalytic Domain; D010450:Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029544:Foot-and-Mouth Disease Virus / Q000201:enzymology* / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010206:Papain / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity
D000600:Amino Acids, Dicarboxylic; D011994:Recombinant Proteins; D001224:Aspartic Acid; D010450:Endopeptidases; D010206:Papain; C088747:leader proteinase, foot-and-mouth disease virus