5ERN: Crystal Structure Of Elongation Domain Of Phomopsis Amygdali Fusicoccadiene Synthase

Fusicoccin A is a diterpene glucoside phytotoxin generated by the fungal pathogen Phomopsis amygdali that causes the plant disease constriction canker, first discovered in New Jersey peach orchards in the 1930s. Fusicoccin A is also an emerging new lead in cancer chemotherapy. The hydrocarbon precursor of fusicoccin A is the tricyclic diterpene fusicoccadiene, which is generated by a bifunctional terpenoid synthase. Here, we report X-ray crystal structures of the individual catalytic domains of fusicoccadiene synthase: the C-terminal domain is a chain elongation enzyme that generates geranylgeranyl diphosphate, and the N-terminal domain catalyzes the cyclization of geranylgeranyl diphosphate to form fusicoccadiene. Crystal structures of each domain complexed with bisphosphonate substrate analogues suggest that three metal ions and three positively charged amino acid side chains trigger substrate ionization in each active site. While in vitro incubations reveal that the cyclase domain can utilize farnesyl diphosphate and geranyl diphosphate as surrogate substrates, these shorter isoprenoid diphosphates are mainly converted into acyclic alcohol or hydrocarbon products. Gel filtration chromatography and analytical ultracentrifugation experiments indicate that full-length fusicoccadiene synthase adopts hexameric quaternary structure, and small-angle X-ray scattering data yield a well-defined molecular envelope illustrating a plausible model for hexamer assembly.
PDB ID: 5ERNDownload
MMDB ID: 135789
PDB Deposition Date: 2015/11/14
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.43  Å
Source Organism:
Similar Structures:
Biological Unit for 5ERN: hexameric; determined by author and by software (PISA)
Molecular Components in 5ERN
Label Count Molecule
Proteins (6 molecules)
Fusicoccadiene Synthase
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB