Unlocking Enzyme Synthesis of Rare Sugars to Create Drugs with Fewer Side Effects

In a paper published in Structure, a team led by the U.S. Department of Energy’s Oak Ridge National Laboratory reported the pioneering use of neutron and X-ray crystallography and high performance computing to study how the enzyme D-xylose isomerase, or XI, can cause a biochemical reaction in natural sugar to produce rare sugars. Unlike drugs made from natural sugar compounds, drugs made from rare sugars do not interfere with cellular processes. As a result, rare sugars have important commercial and biomedical applications as precursors for the synthesis of different antiviral and anti-cancer drugs with fewer side effects. Using X-ray and neutron crystallography combined with theoretical calculations, the team figured out how the enzyme isomerizes L-arabinose into the rare sugar L-ribulose and then epimerizes the latter into another rare sugar L-ribose. Importantly, L-ribose is the enantiomer, a mirror image, of the ubiquitous D-ribose that is a building block of DNA and RNA.

Langan , A.K. Sangha, T. Wymore, J.M. Parks, Z.K. Yang, B.L. Hanson, Z. Fisher, S.A. Mason, M.P. Blakeley, V.T. Forsyth, J.P. Glusker, H.L. Carrell, J.C. Smith, D.A. Keen, D.E. Graham, A. Kovalevsky. “L-Arabinose Binding, Isomerization, and Epimerization by D-Xylose Isomerase: X-Ray/Neutron Crystallographic and Molecular Simulation Study,” Structure. 22:9 (2014): 1287–1300. http://dx.doi.org/10.1016/j.str.2014.07.002