Galactitol-1-phosphate 5-dehydrogenase (GPDH) is a polyol dehydrogenase that catalyses the Zn2+ and NAD+-dependent stereoselective dehydrogenation of L-galactitol-1-phosphate to D-tagatose-6-phosphate. J.M. Mancheño (Dept. of Crystallography) in collaboration with Gert W. Kohring, Federico Gago and Rosario Muñoz, have reported three crystal structures of GPDH from Escherichia coli: the open state with Zn2+ in the catalytic site and also those of the closed state in complex with the polyols Tris and glycerol, respectively, but with no cofactor bound, which contrast with the behaviour of the prototypical mammalian liver alcohol dehydrogenase. Unexpectedly, a large internal cavity was found at the main contacting interface between GPDH subunits (GPDH is a dimer) that probably facilitates their relative movement. The binding mode of the substrate analogue glycerol reveals, for the first time in the polyol dehydrogenases, a penta-coordinated zinc ion in complex with a polyol and also a strong hydrogen bond with the conserved Glu144, an interaction originally proposed more than thirty years ago that supports a catalytic role for this acidic residue.

Rocío Benavente, María Esteban-Torres, Gert-Wieland Kohring, Álvaro Cortés-Cabrera, Pedro A. Sánchez-Murcia, Federico Gago, Iván Acebrón, Blanca De Las Rivas, Rosario Muñoz, José M. Mancheño. “Enantioselective oxidation of galactitol-1-phosphate by galactitol-1-phosphate 5-dehydrogenase from Escherichia coli”. Acta Crystallographica (2015) D71, 1540-1554. 
(doi: 10.1107/S1399004715009281)