Transition-state interactions revealed in purine nucleoside phosphorylase by binding isotope effects

Andrew S. Murkin, Peter C. Tyler, Vern L. Schramm

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Abstract

The binding of [5′-3H]inosine to human purine nucleoside phosphorylase results in an equilibrium binding isotope effect (BIE) of 1.5%, and transition state formation causes an intrinsic KIE of 4.7%. These values reflect atomic vibrational distortions in the 5′-C-H bonds upon formation of the Michaelis complex and transition state. The degree of atomic distortion for catalysis is compared to that for binding of transition state analogues. Similar radiolabeled forms of the transition-state analogues ImmH and DADMe-ImmH gave large 5′-3H BIEs of 12.6% and 29.2%, respectively. Greater bond distortions occur upon complex formation with transition-state analogues, supporting weaker distortional forces at the transition state than in the formation of complexes with transition-state analogues.

Original languageEnglish (US)
Pages (from-to)2166-2167
Number of pages2
JournalJournal of the American Chemical Society
Volume130
Issue number7
DOIs
Publication statusPublished - Feb 20 2008

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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