Constrained Bonding Environment in the Michaelis Complex of Trypanosoma cruzi Uridine Phosphorylase

Rafael G. Silva, D. Randal Kipp, Vern L. Schramm

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The transition state for the Trypanosoma cruzi uridine phosphorylase (TcUP) reaction has an expanded SN2 character. We used binding isotope effects (BIE's) to probe uridine distortion in the complex with TcUP and sulfate to mimic the Michaelis complex. Inverse 1'-3H and 5'- 3H BIE's indicate a constrained bonding environment of these groups in the complex. Quantum chemical modeling identified a uridine conformer whose calculated BIE's match the experimental values. This conformer differs in sugar pucker and uracil orientation from the unbound conformer and the transition-state structure. These results support ground-state stabilization in the Michaelis complex.

Original languageEnglish (US)
Pages (from-to)6715-6717
Number of pages3
JournalBiochemistry
Volume51
Issue number34
DOIs
StatePublished - Aug 28 2012

ASJC Scopus subject areas

  • Biochemistry

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