STRUCTURAL AND MECHANISTIC SIMILARITIES OF 6-PHOSPHOGLUCONATE AND 3-HYDROXYISOBUTYRATE DEHYDROGENASES REVEAL A NEW ENZYME FAMILY, THE 3-HYDROXYACID DEHYDROGENASES

Rat 3-hydroxyisobutyrate dehydrogenase exhibits significant amino acid sequence homology with 6-phosphogluconate dehydrogenase, D-phenylseri ne dehydrogenase from Pseudomonas syringae, and a number of hypothetic al proteins encoded by genes of microbial origin, Rey residues previou sly proposed to have roles in substrate binding and catalysis in sheep 6-phosphogluconate dehydrogenase are highly conserved in this entire family of enzymes, Site-directed mutagenesis, chemical modification, a nd substrate specificity studies were used to compare possible mechani stic similarities of 3-hydroxyisobutyrate dehydrogenase with 6-phospho gluconate dehydrogenase. The data suggest that 3-hydroxyisobutyrate an d 6-phosphogluconate dehydrogenases may comprise, in part, a previousl y unrecognized family of 3-hydroxyacid dehydrogenases.