Leishmania mexicana mexicana glucose-6-phosphate isomerase: crystallization, molecular-replacement solution and inhibition

Glucose‐6‐phosphate isomerase (PGI; EC 5.3.1.9; also often called by its old nomenclature phosphoglucose isomerase) is an intracellular enzyme that catalyses the reversible conversion of d‐­glucose 6‐­phosphate (G6P) to d‐fructose 6‐phosphate (F6P). The native Leishmania PGI is a homodimeric molecule of 60 kDa per monomer with 47% sequence identity to human PGI. It has been shown to be present in both the cytosol and the glycosome of Leishmania promastigotes and represents a potential target for rational drug design. The present work describes the crystallization of two bacterially expressed Leishmania PGI constructs, one corresponding to the natural protein and the other to an N‐terminally deleted form. Crystals of both forms are identical and present a large c unit‐cell parameter. A complete data set was collected from the N‐terminally deleted PGI to a resolution of 3.3 Å in space group P61, with unit‐cell parameters a = b = 87.0, c = 354.7 Å, α = β = 90, γ = 120°. A preliminary study of the first inhibitors to be evaluated on the Leishmania enzyme is also reported.