Cloning, expression, purification, and activity of dog (Canis familiaris) and monkey (Saimiri boliviensis) cathepsin S.
Cathepsin S is the key protease responsible for the removal of the invariant chain from MHC class II molecules and, as such, has attracted much attention as a target for developing immunosuppressive drugs. To help in testing candidate compounds, the monkey (Saimiri boliviensis) and dog (Canis familiaris) cathepsin S cDNAs have been cloned. The monkey cDNA sequence encodes a 330 amino acid protein with 95% homology to human cathepsin S. The dog cDNA sequence encodes a 331 amino acid protein with 91% homology to human cathepsin S. The amino acid differences do not have a major effect on the hydrolysis of the substrate Z-VVR-AMC, but may affect the substrate specificity. As for human and bovine cathepsin S, activity against Z-VVR-AMC extends into the neutral pH range. These parameters are important for understanding the role of cathepsin S in different species and for testing inhibitors in animal models of autoimmunity.
Baker
Sherry M
SM
Johnson and Johnson Pharmaceutical Research and Development, 3210 Merryfield Row, San Diego, CA 92121, USA.
Karlsson
Lars
L
Thurmond
Robin L
RL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002403:Cathepsins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004285:Dogs; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D012453:Saimiri / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D018076:DNA, Complementary; D002403:Cathepsins; C028217:cathepsin S