Open–closed conformational change revealed by the crystal structures of 3-keto-l-gulonate 6-phosphate decarboxylase from Streptococcus mutans

The 3-keto-l-gulonate 6-phosphate decarboxylase (KGPDC) catalyses the decarboxylation of 3-keto-l-gulonate 6-phosphate to l-xylulose in the presence of magnesium ions. The enzyme is involved in l-ascorbate metabolism and plays an essential role in the pathway of glucuronate interconversion. Crystal structures of Streptococcus mutans KGPDC were determined in the absence and presence of the product analog d-ribulose 5-phosphate. We have observed an 8 Å αB-helix movement and other structural rearrangements around the active site between the apo-structures and product analog bound structure. These drastic conformational changes upon ligand binding are the first observation of this kind for the KGPDC family. The flexibilities of both the α-helix lid and the side chains of Arg144 and Arg197 are associated with substrate binding and product releasing. The open–closed conformational changes of the active site, through the movements of the α-helix lid and the arginine residues are important for substrate binding and catalysis.