AI Article Synopsis
- The study examines how protein dynamics over different time scales influence enzyme catalysis, focusing on human purine nucleoside phosphorylase (PNP).
- It was found that isotopic substitution (heavy PNP) reduced the rate of chemistry on the enzyme without changing the transition state structure or steady-state kinetics.
- The research used transition path sampling to analyze atomic motions that enhance barrier crossing in heavy PNP, showing how mass affects specific vibrations that stabilize critical molecular interactions.
Article 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564558 | PMC |
| http://dx.doi.org/10.1021/jz301670s | DOI Listing |
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