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Switching on a Nontraditional Enzymatic Base - Deprotonation by Serine in the ent-Kaurene Synthase from Bradyrhizobium japonicum.

ABSTRACT: Terpene synthases often catalyze complex carbocation cascade reactions. It has been previously shown that single residue switches involving replacement of a key aliphatic residue with serine or threonine can "short-circuit" such reactions, presumed to act indirectly via dipole stabilization of intermediate carbocations. Here a similar switch was found in the structurally characterized ent-kaurene synthase from Bradyrhizobium japonicum. Application of a recently developed computational approach to terpene synthases, TerDockin, surprisingly indicates direct action of the introduced serine hydroxyl as a catalytic base. Notably, this model suggests alternative interpretation of previous results, and potential routes towards reengineering terpene synthase activity more generally.

SUBMITTER: Jia M

PROVIDER: S-EPMC7266162 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Switching on a Nontraditional Enzymatic Base - Deprotonation by Serine in the ent-Kaurene Synthase from Bradyrhizobium japonicum.

Jia Meirong M Zhang Yue Y Siegel Justin B JB Tantillo Dean J DJ Peters Reuben J RJ

ACS catalysis 20190827 10

Terpene synthases often catalyze complex carbocation cascade reactions. It has been previously shown that single residue switches involving replacement of a key aliphatic residue with serine or threonine can "short-circuit" such reactions, presumed to act indirectly via dipole stabilization of intermediate carbocations. Here a similar switch was found in the structurally characterized ent-kaurene synthase from Bradyrhizobium japonicum. Application of a recently developed computatio ...[more]

PMID: 32489716

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