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.
Li
Gui-Lan
GL
The National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Science, Peking University, Beijing 100871, People's Republic of China.
Liu
Xiang
X
Nan
Jie
J
Brostromer
Erik
E
Li
Lan-Fen
LF
Su
Xiao-Dong
XD
D000595:Amino Acid Sequence; D002262:Carboxy-Lyases / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008024:Ligands; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012267:Ribosemonophosphates / Q000737:chemistry*; D013295:Streptococcus mutans / Q000201:enzymology*
D008024:Ligands; D012267:Ribosemonophosphates; C031626:ribose-5-phosphate; D002262:Carboxy-Lyases