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Phosphoglycerate mutase 1 (PGAM1),an important enzyme in glycolysis,is overexpressed in a number of human cancers,thus has been proposed as a promising metabolic target for cancer treatments.The C-terminal portion of the available crystal structures of PGAM1 and its homologous proteins is partially disordered,as evidenced by weak electron density.In this study,we identified the conformational behavior of the C-terminal region of PGAM1 as well as its role during the catalytic cycle.Using the PONDR-FIT server,we demonstrated that the C-terminal region was intrinsically disordered.We applied the Monte Carlo (MC) method to explore the conformational space of the C-terminus and conducted a series of explicit-solvent molecular dynamics (MD) simulations,and revealed that the C-terminal region is inherently dynamic;large-scale conformational changes in the C-terminal segment led to the structural transition of PGAM1 from the closed state to the open state.Furthermore,the C-terminal segment influenced 2,3-bisphosphoglycerate (2,3-BPG) binding.The proposed swing model illustrated a critical role of the C-terminus in the catalytic cycle through the conformational changes.In conclusion,the C-terminal region induces large movements of PGAM1 from the closed state to the open state and influences cofactor binding during the catalytic cycle.This report describes the dynamic features of the C-terminal region in detail and should aid in design of novel and efficient inhibitors of PGAM1.A swing mechanism of the C-terminal region is proposed,to facilitate further studies of the catalytic mechanism and the physiological functions of its homologues.