Atomic detail of chemical transformation at the transition state of an enzymatic reaction
| Autor: | Suwipa Saen-oon, Sara Quaytman-Machleder, Steven D. Schwartz, Vern L. Schramm |
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| Rok vydání: | 2008 |
| Předmět: |
Reaction mechanism
Conformational change Multidisciplinary Protein Conformation Chemistry digestive oral and skin physiology Leaving group Purine nucleoside phosphorylase Photochemistry Vibration Catalysis Ion Kinetics Motion chemistry.chemical_compound Models Chemical Purine-Nucleoside Phosphorylase Nucleophile Chemical physics Physical Sciences Ribose Humans Ribosemonophosphates Transition path sampling Probability |
| Zdroj: | Proceedings of the National Academy of Sciences. 105:16543-16548 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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