TDH – L-Threonine Dehydrogenase

TDH - L-threonine dehydrogenase ribbon and spacefill diagramWe determined the crystal structure of L-threonine dehydrogenase (TDH) from the hyperthermophilic archaeon Thermococcus kodakaraensis (TkTDH) at 2.4Å resolution. TDH is involved in the first of a two-step biochemical pathway for the conversion of the amino acid threonine to glycine, by catalysing the NAD+ dependent metabolism of L-threonine to 2-amino-3-ketobutyrate. It was found that this 350 amino acid enzyme exists as a homo-tetramer, with four subunits present in the asymmetric unit. In all four monomers the co-enzyme NAD+ was found bound at the active site by extensive hydrogen bonds and Van der Waal contacts with the surrounding residues and a conserved water molecule.

What Does TDH Do?

Amino acids are essential for cellular growth, repair, and maintenance, although organisms are unable to synthesise all the ones they need themselves. Whilst they are able to synthesis some from chemicals and amino acids, others must be absorbed through the diet. L-threonine is an indispensable amino acid and under normal conditions is synthesised by microbes from oxaloacetate. Threonine degradation occurs by two major pathways:

  • either it is converted by TDH to 2-amino-3-ketobutyrate, which by the action of 2-amino-3-ketobutyrate CoA ligase, produces glycine and acetyl CoA
  • or alternatively L-serine/threonine dehydratase converts threonine to NH4+ and 2-ketobutyrate and the latter is further metabolised by way of acetyl CoA.

Structure and Function of the L-Threonine Dehydrogenase (TkTDH) from the hyperthermophilic archaeon Thermococcus kodakaraensis
J Struct Biol 2009 Jul 168(2), 294-304
Bowyer A, Mikolajek H, Stuart J.W, Wood S.P, Akhtar M, Cooper J.B.
Crystallisation and preliminary X-ray diffraction analysis of L-Threonine Dehydrogenase (TDH) from the hyperthermophilic archaeon Thermococcus kodakaraensis
Acta Cryst. 2008 Aug 6; F64: 828-830
Bowyer A, Mikolajek H, Wright J.N, Coker A, Cooper J.B, Bashir Q, Rashid N, Jamil F, Akhtar M.