Modification of apolipoprotein C-II with 1,2-cyclohexanedione and 2,3-butanedione. Role of arginine in the activation of lipoprotein lipase.
Apolipoprotein C-II, the activator protein of lipoprotein lipase, contains 78 amino acids with a single residue of arginine at position 49. Chemical modification of apolipoprotein C-II with 1,2-cyclohexanedione or 2,3-butanedione results in a loss of both the arginine residue and the ability of the protein to enhance the activity of bovine milk lipoprotein lipase toward a trioleoylglycerol substrate; removal of the modifying group restores arginine and more than 70% of the activating property of the apolipoprotein. Arginine modification of apolipoprotein C-II does not effect its lipid-binding properties as assessed by its association to sonicated vesicles of dimyristoylphosphatidylcholine. Furthermore, secondary structure associated with complex formation with dimyristoylphosphatidylcholine are nearly identical for the unmodified, 1,2-cyclohexanedione-modified or modified-reversed proteins. These results suggest that arginine-49 of apolipoprotein C-II is situated at or near an amino acid sequence domain involved in the activation of lipoprotein lipase. However, a guanidinium group is not required for lipid binding.
D000818:Animals; D053304:Apolipoprotein C-II; D001053:Apolipoproteins / Q000378:metabolism*; D001056:Apolipoproteins C; D001120:Arginine; D002417:Cattle; D003510:Cyclohexanes / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology*; D004789:Enzyme Activation; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014461:Ultracentrifugation
D053304:Apolipoprotein C-II; D001053:Apolipoproteins; D001056:Apolipoproteins C; D003510:Cyclohexanes; D003512:Cyclohexanones; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; C007366:diepoxybutane; C018031:1,2-cyclohexanedione; D001120:Arginine; D008071:Lipoprotein Lipase