Studies of the coenzyme binding site of rat ovarian 20 alpha-hydroxysteroid dehydrogenase.
Rat ovarian 20 alpha-hydroxysteroid dehydrogenase was shown to be effectively inhibited by adenosine derivatives, nicotinamide derivatives, NADP analogs, N-alkylammonium chlorides, and carboxylic acids through coenzyme-competitive inhibition studies. Multiple inhibition analysis was used to demonstrate either simultaneous binding of inhibitors that interact with different regions of the NADP-binding site or mutual exclusion of inhibitors that interact with the same region on the enzyme. The results of these studies demonstrated that the 2'-phosphate, the pyrophosphate, and the positively charged ring nitrogen are important features of the coenzyme structure in binding to the coenzyme-binding site of the enzyme. In addition, the presence of a hydrophobic region near the NADP-binding site was indicated by positive chainlength effects observed in the binding of nicotinamide derivatives, alkylammonium chlorides, and carboxylic acids.
Pongsawasdi
P
P
Anderson
B M
BM
D015089:20-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002264:Carboxylic Acids / Q000494:pharmacology; D003067:Coenzymes / Q000378:metabolism*; D005260:Female; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010053:Ovary / Q000201:enzymology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats
D002264:Carboxylic Acids; D003067:Coenzymes; D000644:Quaternary Ammonium Compounds; D009536:Niacinamide; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D000241:Adenosine