title: The interaction between Escherichia coli aspartokinase-homoserine dehydrogenase and 3-acetylpyridine-adenine dinucleotide phosphate (reduced), an analog of NADPH.
abstract: The interaction of 3-acetylpyridine-adenine dinucleotide phosphate, a structural analog of NADPH, with aspartokinase-homoserine dehydrogenase has been studied by fluorescence and activity measurements. This analog binds to the same site and with the same affinity as does the natural coenzyme. Also, the binding of homoserine to the dehydrogenase site or that of threonine to the regulatory site is the same whether NADPH or its analog is bound to the enzyme. So NADPH and its analog appear as equivalent in the formation of various stable enzyme-ligand(s) complexes. The analog resembles NADPH enough so that it is a substrate that the enzyme can use to reduce aspartate semialdehyde; the maximum velocity of this dehydrogenase reaction is however reduced by 90% as compared to that with NADPH. It seems as if one of the catalytic steps is affected by the replacement of a--CONH2 group by--COCH3. Another difference between the two coenzymes is that the reaction with the analog is insensitive to threonine, whereas that with NADPH is inhibited. The lack of inhibition is not due to a lack of binding, but rather to a difference in the ternary complexes composed of enzyme, coenzyme, and substrate. A possible relationship between the inhibition by threonine and the mechanism of the dehydrogenase reaction is thus suggested by this comparison between NADPH and its analog.
mesh_terms: D001225:Aspartokinase Homoserine Dehydrogenase / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology*; D007700:Kinetics; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009243:NAD / Q000031:analogs & derivatives* / Q000494:pharmacology; D009249:NADP; D010084:Oxidation-Reduction; D011485:Protein Binding
chemical_list: D009097:Multienzyme Complexes; D009243:NAD; D009249:NADP; C005941:3-acetylpyridine adenine dinucleotide; D001225:Aspartokinase Homoserine Dehydrogenase