Structural characterization of a D-isomer specific 2-hydroxyacid dehydrogenase from Lactobacillus delbrueckii ssp. bulgaricus

J Struct Biol. 2013 Feb;181(2):179-84. doi: 10.1016/j.jsb.2012.10.009. Epub 2012 Oct 27.


Hydroxyacid dehydrogenases, responsible for the stereospecific conversion of 2-keto acids to 2-hydroxyacids in lactic acid producing bacteria, have a range of biotechnology applications including antibiotic synthesis, flavor development in dairy products and the production of valuable synthons. The genome of Lactobacillus delbrueckii ssp. bulgaricus, a member of the heterogeneous group of lactic acid bacteria, encodes multiple hydroxyacid dehydrogenases whose structural and functional properties remain poorly characterized. Here, we report the apo and coenzyme NAD⁺ complexed crystal structures of the L. bulgaricusD-isomer specific 2-hydroxyacid dehydrogenase, D2-HDH. Comparison with closely related members of the NAD-dependent dehydrogenase family reveals that whilst the D2-HDH core fold is structurally conserved, the substrate-binding site has a number of non-canonical features that may influence substrate selection and thus dictate the physiological function of the enzyme.

MeSH terms

  • Alcohol Oxidoreductases / chemistry*
  • Alcohol Oxidoreductases / metabolism
  • Crystallography, X-Ray
  • Isomerism
  • Lactobacillus delbrueckii / enzymology*
  • Models, Molecular*
  • NAD / chemistry
  • NAD / metabolism
  • Protein Binding
  • Protein Conformation*


  • NAD
  • Alcohol Oxidoreductases
  • 2-hydroxyacid dehydrogenase