The human beta 3 alcohol dehydrogenase subunit differs from beta 1 by a Cys for Arg-369 substitution which decreases NAD(H) binding.
The beta 3 beta 3 (formerly called beta Indianapolis) and beta 1 beta 1 isoenzymes of human alcohol dehydrogenase differ substantially in their catalytic properties. Specifically, the KM value for NAD+ of beta 3 beta 3 is 70 times greater than that of beta 1 beta 1, and the Ki value for NADH is 35 times greater than that of beta 1 beta 1. To identify the structural basis of these catalytic differences, we sequenced regions of the beta 3 subunit and the beta 3 gene. beta 3 differs from beta 1 by the substitution of Cys for Arg-369. Based on x-ray crystallography of horse ADH, Arg-369 should interact with the nicotinamide phosphate moiety of NAD(H). The Cys for Arg-369 substitution would decrease the enzyme's affinity for coenzyme and, thus, account for the observed kinetic differences between beta 3 beta 3 and beta 1 beta 1.
D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001120:Arginine; D001665:Binding Sites; D003545:Cysteine; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D046911:Macromolecular Substances; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000032:analysis; D011485:Protein Binding
D007527:Isoenzymes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D009243:NAD; D001120:Arginine; D000426:Alcohol Dehydrogenase; D003545:Cysteine