Characterization of two β-decarboxylating dehydrogenases from Sulfolobus acidocaldarius

Extremophiles. 2016 Nov;20(6):843-853. doi: 10.1007/s00792-016-0872-4. Epub 2016 Sep 2.


Sulfolobus acidocaldarius, a hyperthermoacidophilic archaeon, possesses two β-decarboxylating dehydrogenase genes, saci_0600 and saci_2375, in its genome, which suggests that it uses these enzymes for three similar reactions in lysine biosynthesis through 2-aminoadipate, leucine biosynthesis, and the tricarboxylic acid cycle. To elucidate their roles, these two genes were expressed in Escherichia coli in the present study and their gene products were characterized. Saci_0600 recognized 3-isopropylmalate as a substrate, but exhibited slight and no activity for homoisocitrate and isocitrate, respectively. Saci_2375 exhibited distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. These results suggest that Saci_0600 is a 3-isopropylmalate dehydrogenase for leucine biosynthesis and Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase. The crystal structure of Saci_0600 was determined as a closed-form complex that binds 3-isopropylmalate and Mg2+, thereby revealing the structural basis for the extreme thermostability and novel-type recognition of the 3-isopropyl moiety of the substrate.

Keywords: 3-Isopropylmalate dehydrogenase; Crystal structure; Homoisocitrate dehydrogenase; Isocitrate dehydrogenase; Sulfolobus acidocaldarius; β-Decarboxylating dehydrogenase.

MeSH terms

  • 3-Isopropylmalate Dehydrogenase / genetics*
  • 3-Isopropylmalate Dehydrogenase / metabolism
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Isocitrates / metabolism
  • Magnesium / metabolism
  • Malates / metabolism
  • Protein Binding
  • Sulfolobus acidocaldarius / enzymology*
  • Sulfolobus acidocaldarius / genetics


  • Bacterial Proteins
  • Isocitrates
  • Malates
  • beta-isopropylmalate
  • isocitric acid
  • Isocitrate Dehydrogenase
  • 3-Isopropylmalate Dehydrogenase
  • Magnesium