Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase.
The x-ray crystal structure of dimeric (+)-bornyl diphosphate synthase, a metal-requiring monoterpene cyclase from Salvia officinalis, is reported at 2.0-A resolution. Each monomer contains two alpha-helical domains: the C-terminal domain catalyzes the cyclization of geranyl diphosphate, orienting and stabilizing multiple reactive carbocation intermediates; the N-terminal domain has no clearly defined function, although its N terminus caps the active site in the C-terminal domain during catalysis. Structures of complexes with aza analogues of substrate and carbocation intermediates, as well as complexes with pyrophosphate and bornyl diphosphate, provide "snapshots" of the terpene cyclization cascade.
Whittington
Douglas A
DA
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, USA.
Wise
Mitchell L
ML
Urbansky
Marek
M
Coates
Robert M
RM
Croteau
Rodney B
RB
Christianson
David W
DW
D001665:Binding Sites; D002384:Catalysis; D018076:DNA, Complementary / Q000235:genetics; D019753:Intramolecular Lyases / Q000737:chemistry* / Q000502:physiology; D008958:Models, Molecular; D039821:Monoterpenes / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry* / Q000502:physiology; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D027544:Salvia / Q000201:enzymology*; D013329:Structure-Activity Relationship
D018076:DNA, Complementary; D039821:Monoterpenes; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; D019753:Intramolecular Lyases; C040265:pinene cyclase I