Structural studies of malic enzyme

 

Liang Tong, Department of Biological Sciences, Columbia University, New York, NY, USA

 

Malic enzymes catalyze the oxidative decarboxylation of malate to

produce pyruvate and CO2, with the concomitant reduction of the

dinucleotide cofactor NAD or NADP. The enzymes also require the presence

of divalent cations (Mg or Mn) for their activity. They are widely

distributed in nature and have highly conserved amino acid sequences and

important biological functions. Our structural studies of the human

mitochondrial NAD-dependent malic enzyme have established malic enzymes

as a new class of oxidative decarboxylases, and revealed the binding

modes of the divalent cation, the substrate malate, and the

transition-state analog inhibitors (oxalate, tartronate). Substrate

binding induces a closed form of the enzyme, which may facilitate the

catalysis. Residues Tyr112 and Lys183 are identified to be important for

catalysis by the structural studies. To gain a better understanding of

this important class of enzymes, we have recently determined the crystal

structure of the cytosolic NADP-dependent malic enzyme from pigeon

liver.