Mapping adenosine cyclic 3',5'-phosphate binding sites on type I and type II adenosine cyclic 3',5'-phosphate dependent protein kinases using ribose ring and cyclic phosphate ring analogues of adenosine cyclic 3',5'-phosphate.
A series of adenosine cyclic 3',5'-phosphate (cAMP) derivatives containing modifications or substitutions in either the 2',3',4', or 5' position or the phosphate were examined for their abilities to activate type I isozymes of cAMP-dependent protein kinase (PK I) from rabbit or porcine skeletal muscle and type II isozymes of cAMP-dependent protein kinase (PK II) from bovine brain and heart. The studies revealed that the activation of both PK I and PK II isozymes requires a 2'-hydroxyl group in the ribo configuration, a 3' oxygen in the ribo configuration, and a charged cyclic phosphate. The two isozymes appeared to differ in those portions of their respective cAMP-binding sites that are adjacent to the 4' position of the ribose ring and the 3' position, 5' position, and phosphate portion of the cyclic phosphate ring.
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D002417:Cattle; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004789:Enzyme Activation; D007527:Isoenzymes / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D000242:Cyclic AMP; D011494:Protein Kinases