Bifunctional isocitrate-homoisocitrate dehydrogenase: a missing link in the evolution of beta-decarboxylating dehydrogenase

Biochem Biophys Res Commun. 2005 May 27;331(1):341-6. doi: 10.1016/j.bbrc.2005.03.169.

Abstract

Beta-decarboxylating dehydrogenases comprise 3-isopropylmalate dehydrogenase, isocitrate dehydrogenase, and homoisocitrate dehydrogenase. They share a high degree of amino acid sequence identity and occupy equivalent positions in the amino acid biosynthetic pathways for leucine, glutamate, and lysine, respectively. Therefore, not only the enzymes but also the whole pathways should have evolved from a common ancestral pathway. In Pyrococcus horikoshii, only one pathway of the three has been identified in the genomic sequence, and PH1722 is the sole beta-decarboxylating dehydrogenase gene. The organism does not require leucine, glutamate, or lysine for growth; the single pathway might play multiple (i.e., ancestral) roles in amino acid biosynthesis. The PH1722 gene was cloned and expressed in Escherichia coli and the substrate specificity of the recombinant enzyme was investigated. It exhibited activities on isocitrate and homoisocitrate at near equal efficiency, but not on 3-isopropylmalate. PH1722 is thus a novel, bifunctional beta-decarboxylating dehydrogenase, which likely plays a dual role in glutamate and lysine biosynthesis in vivo.

MeSH terms

  • Alcohol Oxidoreductases / chemistry
  • Alcohol Oxidoreductases / genetics*
  • Alcohol Oxidoreductases / metabolism
  • Amino Acid Sequence
  • Amino Acids / biosynthesis
  • Base Sequence
  • Cloning, Molecular
  • Evolution, Molecular*
  • Gene Expression
  • Isocitrate Dehydrogenase / chemistry
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Molecular Sequence Data
  • Protein Folding
  • Pyrococcus horikoshii / enzymology*
  • Pyrococcus horikoshii / genetics
  • Sequence Alignment
  • Substrate Specificity

Substances

  • Amino Acids
  • Alcohol Oxidoreductases
  • Isocitrate Dehydrogenase
  • homoisocitrate dehydrogenase