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The equilibrium between phosphorylation and dephosphorylation is one of the most important processes that takes place in living cells. Human phosphoserine phosphatase (hPSP) is a key enzyme in the production of serine by the dephosphorylation of phospho-L-serine. It is directly involved in the bio­synthesis of other important metabolites such as glycine and D-serine (a neuromodulator). hPSP is involved in the survival mechanism of cancer cells and has recently been found to be an essential biomarker. Here, three new high-resolution crystal structures of hPSP (1.5–2.0 Å) in complexes with phosphoserine and with serine, which are the substrate and the product of the reaction, respectively, and in complex with a noncleavable substrate analogue (homocysteic acid) are presented. New types of interactions take place between the enzyme and its ligands. Moreover, the loop involved in the open/closed state of the enzyme is fully refined in a totally unfolded conformation. This loop is further studied through molecular-dynamics simulations. Finally, all of these analyses allow a more complete reaction mechanism for this enzyme to be proposed which is consistent with previous publications on the subject.

Supporting information

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Portable Document Format (PDF) file https://doi.org/10.1107/S2059798319006867/di5029sup1.pdf
Distances tables, structures comparison with other PSPs, technical details regarding the ligand structure building and description of the molecular-dynamics calculations.

PDB references: phosphoserine phosphatase, complex with phosphoserine, 6hyj; complex with serine, 6hyy; complex with homocysteic acid, 6q6j


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