8V0F

Cryo-EM structure of the unliganded hexameric prenyltransferase in bifunctional copalyl diphosphate synthase from Penicillium fellutanum with an open conformation

Summary for 8V0F

• Entry DOI: 10.2210/pdb8v0f/pdb
• EMDB information: 42853
• Descriptor: Copalyl diphosphate synthase (1 entity in total)
• Functional Keywords: terpene, biosynthesis, enzyme, transferase
• Biological source: Penicillium fellutanum ATCC 48694
• Total number of polymer chains: 6
• Total formula weight: 650904.42

Authors

Gaynes, M.N.,Christianson, D.W. (deposition date: 2023-11-17, release date: 2024-01-17, Last modification date: 2024-01-24)

Primary citation

Gaynes, M.N.,Ronnebaum, T.A.,Schultz, K.,Faylo, J.L.,Marmorstein, R.,Christianson, D.W.
Structure of the prenyltransferase in bifunctional copalyl diphosphate synthase from Penicillium fellutanum reveals an open hexamer conformation.
J.Struct.Biol., 216:108060-108060, 2024

PubMed Abstract: Copalyl diphosphate synthase from Penicillium fellutanum (PfCPS) is an assembly-line terpene synthase that contains both prenyltransferase and class II cyclase activities. The prenyltransferase catalyzes processive chain elongation reactions using dimethylallyl diphosphate and three equivalents of isopentenyl diphosphate to yield geranylgeranyl diphosphate, which is then utilized as a substrate by the class II cyclase domain to generate copalyl diphosphate. Here, we report the 2.81 Å-resolution cryo-EM structure of the hexameric prenyltransferase of full-length PfCPS, which is surrounded by randomly splayed-out class II cyclase domains connected by disordered polypeptide linkers. The hexamer can be described as a trimer of dimers; surprisingly, one of the three dimer-dimer interfaces is separated to yield an open hexamer conformation, thus breaking the D3 symmetry typically observed in crystal structures of other prenyltransferase hexamers such as wild-type human GGPP synthase (hGGPPS). Interestingly, however, an open hexamer conformation was previously observed in the crystal structure of D188Y hGGPPS, apparently facilitated by hexamer-hexamer packing in the crystal lattice. The cryo-EM structure of the PfCPS prenyltransferase hexamer is the first to reveal that an open conformation can be achieved even in the absence of a point mutation or interaction with another hexamer. Even though PfCPS octamers are not detected, we suggest that the open hexamer conformation represents an intermediate in the hexamer-octamer equilibrium for those prenyltransferases that do exhibit oligomeric heterogeneity.

PubMed: 38184156
DOI: 10.1016/j.jsb.2023.108060

Experimental method

ELECTRON MICROSCOPY (2.81 Å)