Atomic detail of chemical transformation at the transition state of an enzymatic reaction

Suwipa Saen-oon, Sara Quaytman-Machleder, Vern L. Schramm, Steven D. Schwartz

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Transition path sampling (TPS) has been applied to the chemical step of human purine nucleoside phosphorylase (PNP). The transition path ensemble provides insight into the detailed mechanistic dynamics and atomic motion involved in transition state passage. The reaction mechanism involves early loss of the ribosidic bond to form a transition state with substantial ribooxacarbenium ion character, followed by dynamic motion from the enzyme and a conformational change in the ribosyl group leading to migration of the anomeric carbon toward phosphate, to form the product ribose 1-phosphate. Calculations of the commitment probability along reactive paths demonstrated the presence of a broad energy barrier at the transition state. TPS identified (i) compression of the O4′⋯O5′ vibrational motion, (ii) optimized leaving group interactions, and (iii) activation of the phosphate nucleophile as the reaction proceeds through the transition state region. Dynamic motions on the femtosecond timescale provide the simultaneous optimization of these effects and coincide with transition state formation.

Original languageEnglish (US)
Pages (from-to)16543-16548
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
StatePublished - Oct 28 2008


  • Dynamics in catalysis
  • Promoting vibrations
  • Purine nucleoside phosphorylase
  • Transition path sampling
  • Transition state lifetime

ASJC Scopus subject areas

  • General


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