7JTH

Cryo-EM structure of unliganded octameric prenyltransferase domain of Phomopsis amygdali fusicoccadiene synthase

Summary for 7JTH

• Entry DOI: 10.2210/pdb7jth/pdb
• EMDB information: 22473
• Descriptor: Fusicoccadiene synthase (1 entity in total)
• Functional Keywords: ggpp synthase, prenyltransferase, transferase, lyase
• Biological source: Phomopsis amygdali
• Total number of polymer chains: 8
• Total formula weight: 671055.13

Authors

Faylo, J.L.,van Eeuwen, T.,Murakami, K.,Christianson, D.W. (deposition date: 2020-08-17, release date: 2021-04-28, Last modification date: 2024-05-29)

Primary citation

Faylo, J.L.,van Eeuwen, T.,Kim, H.J.,Gorbea Colon, J.J.,Garcia, B.A.,Murakami, K.,Christianson, D.W.
Structural insight on assembly-line catalysis in terpene biosynthesis.
Nat Commun, 12:3487-3487, 2021

PubMed Abstract: 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.

PubMed: 34108468
DOI: 10.1038/s41467-021-23589-9

Experimental method

ELECTRON MICROSCOPY (4 Å)