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 A alphaB-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 alpha-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 alpha-helix lid and the arginine residues are important for substrate binding and catalysis.