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Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop

Abstract

Crystal structures of substrate-free and XMP-soaked hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase) of the opportunistic pathogen Toxoplasma gondii have been determined to 2.4 and 2.9 Å resolution, respectively. HGXPRTase displays the conserved PRTase fold. In the structure of the enzyme bound to its product, a long flexible loop (residues 115–126) is located away from the active site. Comparison to the substrate-free structure reveals a striking relocation of the loop, which is poised to cover the catalytic pocket, thus providing a mechanism by which the HG(X)PRTases shield their oxocarbonium transition states from nucleophilic attack by the bulk solvent. The conserved Ser 117-Tyr 118 dipeptide within the loop is brought to the active site, completing the ensemble of catalytic residues.

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Schumacher, M., Carter, D., Roos, D. et al. Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop. Nat Struct Mol Biol 3, 881–887 (1996). https://doi.org/10.1038/nsb1096-881

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