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

Maria A. Schumacher, Darrick Carter, David S. Roos, Buddy Ullman, Richard G. Brennan

Research output: Contribution to journalReview article

93 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)881-887
Number of pages7
JournalNature Structural Biology
Volume3
Issue number10
DOIs
StatePublished - Oct 1 1996

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

Fingerprint Dive into the research topics of 'Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop'. Together they form a unique fingerprint.

  • Cite this