CRYSTAL-STRUCTURES OF TOXOPLASMA-GONDII HGXPRTASE REVEAL THE CATALYTIC ROLE OF A LONG FLEXIBLE LOOP

Crystal structures of substrate-free and XMP-soaked hypoxanthine-guani ne-xanthine phosphoribosyltransferase (HGXPRTase) of the opportunistic pathogen Toxoplasma gondii have been determined to 2.4 and 2.9 Angstr om resolution, respectively. HGXPRTase displays the conserved PRTase f old. In the structure of the enzyme bound to its product, a long flexi ble loop (residues 115-126) is located away from the active site. Comp arison to the substrate-free structure reveals a striking relocation o f the loop, which is poised to cover the catalytic pocket, thus provid ing a mechanism by which the HC(X)PRTases shield their oxocarbonium tr ansition states from nucleophilic attack by the bu Ik solvent. The con served Ser 117-Tyr 118 dipeptide within the loop is brought to the act ive site, completing the ensemble of catalytic residues.