Molecular dynamics study of taxadiene synthase catalysis

Andrés M. Escorcia, Jeaphianne P.M. van Rijn, Gui Juan Cheng, Patrick Schrepfer, Thomas B. Brück, Walter Thiel

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 languageEnglish
Pages (from-to)1215-1225
Number of pages11
JournalJournal of Computational Chemistry
Volume39
Issue number19
DOIs
StatePublished - 15 Jul 2018

Keywords

  • carbocation tumbling
  • enzyme promiscuity
  • enzyme-substrate complexes
  • terpene synthase
  • water bridges

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