A Dianionic Phosphorane Intermediate and Transition States in an Associative AN+DN Mechanism for the RibonucleaseA Hydrolysis Reaction
Journal Article
·
· Journal of the American Chemical Society
- Univ. of California, San Diego, CA (United States)
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
The ubiquitous presence of phosphoryl transfer as central step in many metabolic, signaling, energy storage, etc. enzymatic reactions requires that the details of the reaction mechanisms (e.g. reaction paths, transition state stabilization and structure, etc.) that leads to their remarkable rates in protein catalytic environments be understood1. It is expected that most of these reactions proceed through a pathway that includes a penta- coordinated phosphorane species. However, the nature of the bonding and the protonation of the structure in this region and the possibility of stable intermediates as the system passes along the reaction path through the transitions state (TS) are currently topics of considerable debate1a,b,c. Typically nucleophilic substitution reactions are classified in terms of extremes of two bonding situations along the reaction path: in a dissociative mechanism the substrate phosphate bridging bond is broken and the bond to the entering nucleophilic group is not yet formed leaving a metastable metaphosphate (PO3-) intermediate (a DN+AN reaction); in an associative mechanism in the extreme case a metastable pentacoordinated phosphorane species with nearly equivalent bonds is present in the TS, whose subsequent dissociation leads to the product state (an AN+DN reaction). Recently we published a computational study of the phosphoryl transfer step of a major class of enzymes, the serine kinases2a,b involved in signal transduction. These calculations2b support a dissociative mechanism (DNAN,) for this family of enzymes with unstable metaphosphate structure in loose transition state with total bond order of 22%.
- Research Organization:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States), Environmental Molecular Sciences Laboratory (EMSL)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 951821
- Report Number(s):
- PNNL-SA--58125; 20900; 20904; KP1704020
- Journal Information:
- Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 11 Vol. 131; ISSN JACSAT; ISSN 0002-7863
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
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