Within the scope of improving the efficiency of pancreatic enzyme replacement therapy in cystic fibrosis, the feasibility of shifting the pH-activity profile of pancreatic lipase toward acidic values was investigated by site specific mutagenesis in different regions of the catalytic cavity. We have shown that introducing a negative charge close to the catalytic histidine induced a shift of the pH optimum toward acidic values but strongly reduced the lipase activity. On the other hand, a negative charge in the entrance of the catalytic cleft gives rise to a lipase with improved properties and twice more active than the native enzyme at acidic pH.
        
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Colin DY, Deprez-Beauclair P, Allouche M, Brasseur R, Kerfelec B (2008) Exploring the active site cavity of human pancreatic lipase Biochemical & Biophysical Research Communications370: 394-8
Colin DY, Deprez-Beauclair P, Allouche M, Brasseur R, Kerfelec B (2008) Biochemical & Biophysical Research Communications370: 394-8