Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop.
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 A 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.
Schumacher
M A
MA
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
Carter
D
D
Roos
D S
DS
Ullman
B
B
Brennan
R G
RG
D000818:Animals; D001665:Binding Sites; D010430:Pentosyltransferases / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013379:Substrate Specificity; D014122:Toxoplasma / Q000201:enzymology*
D010430:Pentosyltransferases; C083867:hypoxanthine-guanine-xanthine phosphoribosyltransferase