Increased activity of porcine pancreatic phospholipase A2 by designed long-range electrostatic stabilisation of the transition state.
Stabilisation of the catalytic transition state by long-range charge interactions has been tested with mutagenesis for porcine pancreatic phospholipase A2. Electrostatics calculations were used to determine locations which would interact preferentially with one part of the dipolar charge separation that is believed to develop in the transition state. Experiment shows increased enzyme activity relative to wild-type recombinant enzyme for mutants N97D and N101D, consistent with the design.
D000818:Animals; D001665:Binding Sites; D004563:Electrochemistry; D004795:Enzyme Stability; D008823:Micelles; D008958:Models, Molecular; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D010179:Pancreas / Q000201:enzymology*; D010741:Phospholipases A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine
D008823:Micelles; D011994:Recombinant Proteins; D010741:Phospholipases A; D054467:Phospholipases A2