Mass modulation of protein dynamics associated with barrier crossing in purine nucleoside phosphorylase

Dimitri Antoniou, Xiaoxia Ge, Vern L. Schramm, Steven D. Schwartz

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The role of protein dynamics on different time scales in enzyme catalysis remains an area of active debate. The connection between enzyme dynamics on the femtosecond time scale and transition state formation has been demonstrated in human purine nucleoside phosphorylase (PNP) through the study of a mass-altered enzyme. Isotopic substitution in human PNP (heavy PNP) decreased the rate of on-enzyme chemistry but did not alter either the transition state structure or steady-state kinetic parameters. Here we investigate the underlying atomic motions associated with altered barrier crossing probability for heavy PNP. Transition path sampling was employed to illuminate the molecular differences between barrier crossing in light and heavy enzymes. The mass effect is apparent in promoting vibrations that polarize the N-ribosidic bond, and that promote the stability of the purine leaving group. These motions facilitate barrier crossing.

Original languageEnglish (US)
Pages (from-to)3538-3544
Number of pages7
JournalJournal of Physical Chemistry Letters
Volume3
Issue number23
DOIs
StatePublished - Dec 6 2012

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Purine-Nucleoside Phosphorylase
purines
nucleosides
enzymes
Enzymes
Modulation
proteins
Proteins
modulation
Kinetic parameters
Catalysis
catalysis
Substitution reactions
sampling
Nucleosides
substitutes
chemistry
Sampling
vibration
kinetics

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Mass modulation of protein dynamics associated with barrier crossing in purine nucleoside phosphorylase. / Antoniou, Dimitri; Ge, Xiaoxia; Schramm, Vern L.; Schwartz, Steven D.

In: Journal of Physical Chemistry Letters, Vol. 3, No. 23, 06.12.2012, p. 3538-3544.

Research output: Contribution to journalArticle

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