Abstract
Molecular dynamics (MD) simulations have been performed to study the dynamic behavior of noncovalent enzyme carbocation complexes involved in the cyclization of geranylgeranyl diphosphate to taxadiene catalyzed by taxadiene synthase (TXS). Taxadiene and the observed four side products originate from the deprotonation of carbocation intermediates. The MD simulations of the TXS carbocation complexes provide insights into potential deprotonation mechanisms of such carbocations. The MD results do not support a previous hypothesis that carbocation tumbling is a key factor in the deprotonation of the carbocations by pyrophosphate. Instead water bridges are identified which may allow the formation of side products via multiple proton transfer reactions. A novel reaction path for taxadiene formation is proposed on the basis of the simulations.
Original language | English |
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Pages (from-to) | 1215-1225 |
Number of pages | 11 |
Journal | Journal of Computational Chemistry |
Volume | 39 |
Issue number | 19 |
DOIs | |
State | Published - 15 Jul 2018 |
Keywords
- carbocation tumbling
- enzyme promiscuity
- enzyme-substrate complexes
- terpene synthase
- water bridges