Predicting Productive Binding Modes for Substrates and Carbocation Intermediates in Terpene Synthases-Bornyl Diphosphate Synthase as a Representative Case.

ABSTRACT: Terpene synthases comprise a family of enzymes that convert acyclic oligo-isoprenyl diphosphates to terpene natural products with complex, polycyclic carbon backbones via the generation and protection of carbocation intermediates. To accommodate this chemistry, terpene synthase active sites generally are lined with alkyl and aromatic, i.e., nonpolar, sidechains. Predicting the correct, mechanistically relevant binding modes for entire terpene synthase reaction pathways remains an unsolved challenge. Here we describe a method for identifying such modes: TerDockin, a series of protocols to predict the orientation of carbon skeletons of substrates and derived carbocations relative to the bound diphosphate group in terpene synthase active sites. Using this recipe for bornyl diphosphate

SUBMITTER: O'Brien TE 

PROVIDER: S-EPMC6049084 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature