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

John W. Hawes, Edwin T. Harper, David Crabb, Robert Harris

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)263-267
Number of pages5
JournalFEBS Letters
Volume389
Issue number3
DOIs
StatePublished - Jul 8 1996

Fingerprint

3-hydroxyisobutyrate dehydrogenase
Phosphogluconate Dehydrogenase
Oxidoreductases
Enzymes
Microbial Genes
Pseudomonas syringae
Amino Acid Sequence Homology
Mutagenesis
Chemical modification
Substrates
Substrate Specificity
Site-Directed Mutagenesis
Catalysis
Rats
Sheep
Genes
Amino Acids
6-phosphogluconic acid

Keywords

  • 3-Hydroxyisobutyrate
  • 6-Phosphogluconate
  • Dehydrogenase
  • Pyridoxal phosphate

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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abstract = "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.",
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T1 - Structural and mechanistic similarities of 6-phosphogluconate and 3- hydroxyisobutyrate dehydrogenases reveal a new enzyme family, the 3- hydroxyacid dehydrogenases

AU - Hawes, John W.

AU - Harper, Edwin T.

AU - Crabb, David

AU - Harris, Robert

PY - 1996/7/8

Y1 - 1996/7/8

N2 - 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.

AB - 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.

KW - 3-Hydroxyisobutyrate

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KW - Dehydrogenase

KW - Pyridoxal phosphate

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