Structural analogies between protein kinase C activators.
Phorbol esters and diacylglycerols activate protein kinase C but specific structural parameters appear to be required for the enzyme activation. We have analyzed the conformation of potent and not potent diacylglycerols and phorbol esters. The orientation of the CH20H group at C3 of 1,2 diolein is remarkably similar to that of the same group at C-20 of 4 beta phorbol didecanoate and crucial for potency in activating the enzyme. Our data suggest that the new conformational approach here described could be used to rationally design specific inhibitors preventing the effects of tumor promoters and to predict the structure of potential tumor promoters.
Brasseur
R
R
Cabiaux
V
V
Huart
P
P
Castagna
M
M
Baztar
S
S
Ruysschaert
J M
JM
D000107:Acetylation; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005989:Glycerides / Q000494:pharmacology*; D008968:Molecular Conformation; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D011663:Pulmonary Surfactants; D013329:Structure-Activity Relationship
D004075:Diglycerides; D005989:Glycerides; D010703:Phorbol Esters; D010704:Phorbols; D011663:Pulmonary Surfactants; C008876:phorbol-12,13-didecanoate; C032481:1,3-dioctadecanoylglycerol; D011494:Protein Kinases; D011493:Protein Kinase C; C013965:diolein