Structural studies of the human glyoxylate reductase/hydroxypyruvate reductase (GRHPR) and other proteins

Human glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is a D-2-hydroxyacid dehydrogenase found predominantly within the liver, and is essential for the removal of the reactive metabolic product glyoxylate. Primary hyperoxaluria type 2 (PH2) disease, which is characterised by increased urinary oxalate and L-glycerate levels leading to calcium oxalate deposition and decreased renal function, is caused by mutations in the gene for GRHPR. In this study the first crystal structures of the human GRHPR enzyme are reported. Structures of apo, binary and ternary forms of GRHPR are reported, the latter being the first structure of a true ternary complex of an enzyme from the D-2-hydroxyacid dehydrogenase family.