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Cofactor-independent phosphoglycerate mutase (iPGM), an important enzyme in glycolysis and gluconeogenesis, catalyses the isomerization of 2- and 3-phosphoglycerates by an Mn(2+)-dependent phospho-transfer mechanism via a phospho-enzyme intermediate. Crystal structures of bi-domain iPGM from Staphylococcus aureus, together with substrate-bound forms, have revealed a new conformation of the enzyme, representing an intermediate state of domain movement. The substrate-binding site and the catalytic site are present in two distinct domains in the intermediate form. X-ray crystallography complemented by simulated dynamics has enabled delineation of the complete catalytic cycle, which includes binding of the substrate, followed by its positioning into the catalytic site, phospho-transfer and finally product release. The present work describes a novel mechanism of domain movement controlled by a hydrophobic patch that is exposed on domain closure and acts like a spring to keep the protein in open conformation. Domain closing occurs after substrate binding, and is essential for phospho-transfer, whereas the open conformation is a prerequisite for efficient substrate binding and product dissociation. A new model of catalysis has been proposed by correlating the hinge-bending motion with the phospho-transfer mechanism.

Original publication




Journal article



Publication Date





1097 - 1110


Staphylococcus aureus, X-ray diffraction, catalytic mechanism, cofactor-independent phosphoglycerate mutase, hinge-bending motion, Catalysis, Catalytic Domain, Computer Simulation, Crystallography, X-Ray, Ligands, Manganese, Models, Molecular, Motion, Phosphoglycerate Mutase, Protein Binding, Staphylococcus aureus, Substrate Specificity, Thermodynamics, X-Ray Diffraction