Identification of critical amino acids within the foot-and-mouth disease virus leader protein, a cysteine protease.
The Leader protein of foot-and-mouth disease virus (FMDV) is the first component of the virus polyprotein. It is synthesized in two forms, Lab and Lb, both of which display the ability to cleave the L/P1 junction in trans and to induce the cleavage of the cap-binding complex component eIF-4G (p220). The L protease has weak homology to the family of cysteine proteases, which have a catalytic dyad composed of a cysteine and a histidine. Mutations have been introduced into FMDV cDNA to modify each of the four cysteine residues and the three conserved histidine residues within the Lb species. The activities of the mutant L proteins have been determined. Modification of a single cysteine residue (residue 51) or of a single histidine residue (residue 148) abolished the abilities of L to cleave the L/P1 junction and to inhibit cap-dependent protein synthesis. In contrast, modification of each of the other cysteine residues and other conserved histidine residues had no apparent effect on these activities.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005537:Aphthovirus / Q000201:enzymology*; D001483:Base Sequence; D003545:Cysteine / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006168:Guinea Pigs; D006639:Histidine / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D021382:Protein Sorting Signals / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000596:Amino Acids; D017931:DNA Primers; D004279:DNA, Viral; D021382:Protein Sorting Signals; D006639:Histidine; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C088747:leader proteinase, foot-and-mouth disease virus; D003545:Cysteine