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Structural and mechanistic similarities of 6‐phosphogluconate and 3‐hydroxyisobutyrate dehydrogenases reveal a new enzyme family, the 3‐hydroxyacid dehydrogenases
Author(s) -
Hawes John W.,
Harper Edwin T.,
Crabb David W.,
Harris Robert A.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00597-2
Subject(s) - enzyme , biology , computational biology , biochemistry , genetics , chemistry
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.