1H-NMR and protection studies of interactions between ligands and bovine pancreatic phospholipase A2.
A number of long-chain amines and naphthylamine sulfonates have been studied for their ability to inhibit bovine pancreatic phospholipase A2 (PLA2) and to protect PLA2 against alkylation of the active site histidine by p-bromophenacyl bromide. Their areas of interaction on the enzyme were further delineated using observations of chemical shift changes of assigned aromatic signals in the 1H-NMR spectrum of PLA2, while the bound conformations of two amine inhibitors were revealed using transferred nuclear Overhauser effects. The alkyl amines bind rather non-specifically on the surface of the enzyme, over the active site cleft and the interface recognition site.
Williamson
M P
MP
Roche Products Ltd., Welwyn Garden City, U.K.
Davis
P D
PD
Broadhurst
M J
MJ
Nixon
J S
JS
D000588:Amines / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D008024:Ligands / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009282:Naphthalenesulfonates / Q000378:metabolism / Q000494:pharmacology; D010179:Pancreas / Q000201:enzymology; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2
D000588:Amines; D008024:Ligands; D009282:Naphthalenesulfonates; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2