The ligand specificity of the (adenosine 3',5'-monophosphate)-binding site of yeast glyceraldehyde-3-phosphate dehydrogenase. Interaction with adenosine derivatives and pharmacologically-active compounds.
The high-affinity cAMP-binding site of form-II yeast glyceraldehyde-3-phosphate dehydrogenase has a marked specificity for adenosine derivatives, such ligands including N6-substituted adenosine derivatives active as cytokinins n plant systems and adenine nucleotides. Of a wide range of nucleotides and nucleosides examined only adenosine derivatives bind to the cAMP binding site. A variety of antimitotic compounds (including colchicine, colcemid and phenylcarbamate derivatives), adrenergic receptor antagonists (alprenolol and propranolol) and non-steroidal anti-inflammatory agents (notably indomethacin and flufenamic acid) displace cAMP from glyceraldehyde-3-phosphate dehydrogenase. Colchicine, colcemid, N6-furfuryladenosine, indomethacin, flufenamic acid and propranolol inhibit cAMP binding to the enzyme in an apparently competitive fashion. Given the evolutionary conservatism and abundance of glyceraldehyde-3-phosphate dehydrogenase, the affinity of the cAMP-binding site of this enzyme for a variety of structurally-disparate pharmacologically-active compounds compromises simple one-site interpretations of physiological responses to these agents.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D001667:Binding, Competitive; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D011953:Receptors, Cyclic AMP / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013379:Substrate Specificity
D008024:Ligands; D011953:Receptors, Cyclic AMP; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D000241:Adenosine