Site-specific mutagenesis of the catalytic subunit of cholera toxin: substituting lysine for arginine 7 causes loss of activity.
Cholera and pertussis toxins each contain a subunit with ADP-ribosyltransferase activity, sharing a region of nearly identical amino acid sequence near the NH2 terminus. Previous investigations have shown that substitution of a lysine residue for Arg-9 in the catalytic A subunit of pertussis toxin substantially eliminates its enzyme activity. We now report that substitution of lysine for the position-equivalent Arg-7 of cholera toxin subunit A leads to a similar loss of catalytic activity. This result suggests a correlation of function with structure between the sequence-related cholera and pertussis toxin A subunits and may contribute to the design of a vaccine containing an enzymatically inert analog of cholera toxin.
Amgen Inc., Thousand Oaks, California 91320.
W N
WN
Burnette
V L
VL
Mar
B W
BW
Platler
J D
JD
Schlotterbeck
M D
MD
McGinley
K S
KS
Stoney
M F
MF
Rohde
H R
HR
Kaslow
D001120:Arginine / Q000737:chemistry; D002772:Cholera Toxin / Q000235:genetics* / Q000633:toxicity; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D008239:Lysine / Q000737:chemistry; D009243:NAD / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000633:toxicity; D013329:Structure-Activity Relationship
D011994:Recombinant Proteins; D009243:NAD; D002772:Cholera Toxin; D001120:Arginine; D011065:Poly(ADP-ribose) Polymerases; D008239:Lysine