Catalytic activity of bovine seminal ribonuclease is essential for its immunosuppressive and other biological activities

Abstract
Bovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with special biological properties, including potent immunosuppressive activity. A mutant BS-RNase was created in which His-119, the active-site residue that acts as a general acid during catalysis, was changed to an aspartic acid. H119D BS-RNase formed a dimer with quaternary structure similar to that of the wild-type enzyme but with values of kcat. and kcat./Km for the cleavage of UpA [uridylyl(3′-->5′)adenosine] that were 4 x 10(3)-fold lower. The mutant protein also demonstrated dramatically decreased immunosuppressive, anti-tumour, aspermatogenic, and embryotoxic activities. The catalytic activity of BS-RNase is therefore necessary for its special biological properties.