Structural and mechanistic similarities of 6-phosphogluconate and 3-hydroxyisobutyrate dehydrogenases reveal a new enzyme family, the 3-hydroxyacid dehydrogenases

FEBS Lett. 1996 Jul 8;389(3):263-7. doi: 10.1016/0014-5793(96)00597-2.


Rat 3-hydroxyisobutyrate dehydrogenase exhibits significant amino acid sequence homology with 6-phosphogluconate dehydrogenase, D-phenylserine dehydrogenase from Pseudomonas syringae, and a number of hypothetical proteins encoded by genes of microbial origin. Key residues previously 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, and substrate specificity studies were used to compare possible mechanistic similarities of 3-hydroxyisobutyrate dehydrogenase with 6-phosphogluconate dehydrogenase. The data suggest that 3-hydroxyisobutyrate and 6-phosphogluconate dehydrogenases may comprise, in part, a previously unrecognized family of 3-hydroxyacid dehydrogenases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcohol Oxidoreductases / chemistry*
  • Alcohol Oxidoreductases / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Conserved Sequence
  • Enzyme Inhibitors / pharmacology
  • Evolution, Molecular
  • Kinetics
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphogluconate Dehydrogenase / chemistry*
  • Phosphogluconate Dehydrogenase / metabolism
  • Pseudomonas / enzymology
  • Pyridoxal Phosphate / pharmacology
  • Rats
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity


  • Enzyme Inhibitors
  • Recombinant Proteins
  • Pyridoxal Phosphate
  • Alcohol Oxidoreductases
  • 3-hydroxyisobutyrate dehydrogenase
  • Phosphogluconate Dehydrogenase