National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM56838
米国
引用
ジャーナル: Nat Commun / 年: 2021 タイトル: Structural insight on assembly-line catalysis in terpene biosynthesis. 著者: Jacque L Faylo / Trevor van Eeuwen / Hee Jong Kim / Jose J Gorbea Colón / Benjamin A Garcia / Kenji Murakami / David W Christianson / 要旨: Fusicoccadiene synthase from Phomopsis amygdali (PaFS) is a unique bifunctional terpenoid synthase that catalyzes the first two steps in the biosynthesis of the diterpene glycoside Fusicoccin A, a ...Fusicoccadiene synthase from Phomopsis amygdali (PaFS) is a unique bifunctional terpenoid synthase that catalyzes the first two steps in the biosynthesis of the diterpene glycoside Fusicoccin A, a mediator of 14-3-3 protein interactions. The prenyltransferase domain of PaFS generates geranylgeranyl diphosphate, which the cyclase domain then utilizes to generate fusicoccadiene, the tricyclic hydrocarbon skeleton of Fusicoccin A. Here, we use cryo-electron microscopy to show that the structure of full-length PaFS consists of a central octameric core of prenyltransferase domains, with the eight cyclase domains radiating outward via flexible linker segments in variable splayed-out positions. Cryo-electron microscopy and chemical crosslinking experiments additionally show that compact conformations can be achieved in which cyclase domains are more closely associated with the prenyltransferase core. This structural analysis provides a framework for understanding substrate channeling, since most of the geranylgeranyl diphosphate generated by the prenyltransferase domains remains on the enzyme for cyclization to form fusicoccadiene.
名称: Phomopsis amygdali fusicoccadiene synthase (PaFS) / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: PaFS octameric prenyltransferase domain is well-resolved in structure, with some density for a variably positioned cyclase domain alongside the octamer. Molecular weight reflects the ...詳細: PaFS octameric prenyltransferase domain is well-resolved in structure, with some density for a variably positioned cyclase domain alongside the octamer. Molecular weight reflects the calculated molecular weight of a prenyltransferase octamer plus one cyclase domain.