3BNY

Crystal structure of aristolochene synthase complexed with 2-fluorofarnesyl diphosphate (2F-FPP)

Summary for 3BNY

• Entry DOI: 10.2210/pdb3bny/pdb
• Related: 2E4O 2OA6 3BNX
• Descriptor: Aristolochene synthase, (2Z,6E)-2-fluoro-3,7,11-trimethyldodeca-2,6,10-trien-1-yl trihydrogen diphosphate, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: sesquiterpene cyclase, isoprenoid, farnesyl diphosphate, magnesium, cyclization, lyase
• Biological source: Aspergillus terreus
• Total number of polymer chains: 4
• Total formula weight: 147990.29

Authors

Shishova, E.Y.,Christianson, D.W. (deposition date: 2007-12-14, release date: 2008-03-25, Last modification date: 2023-08-30)

Primary citation

Shishova, E.Y.,Yu, F.,Miller, D.J.,Faraldos, J.A.,Zhao, Y.,Coates, R.M.,Allemann, R.K.,Cane, D.E.,Christianson, D.W.
X-ray Crystallographic Studies of Substrate Binding to Aristolochene Synthase Suggest a Metal Ion Binding Sequence for Catalysis
J.Biol.Chem., 283:15431-15439, 2008

PubMed Abstract: The universal sesquiterpene precursor, farnesyl diphosphate (FPP), is cyclized in an Mg(2+)-dependent reaction catalyzed by the tetrameric aristolochene synthase from Aspergillus terreus to form the bicyclic hydrocarbon aristolochene and a pyrophosphate anion (PP(i)) coproduct. The 2.1-A resolution crystal structure determined from crystals soaked with FPP reveals the binding of intact FPP to monomers A-C, and the binding of PP(i) and Mg(2+)(B) to monomer D. The 1.89-A resolution structure of the complex with 2-fluorofarnesyl diphosphate (2F-FPP) reveals 2F-FPP binding to all subunits of the tetramer, with Mg(2+)(B)accompanying the binding of this analogue only in monomer D. All monomers adopt open activesite conformations in these complexes, but slight structural changes in monomers C and D of each complex reflect the very initial stages of a conformational transition to the closed state. Finally, the 2.4-A resolution structure of the complex with 12,13-difluorofarnesyl diphosphate (DF-FPP) reveals the binding of intact DF-FPP to monomers A-C in the open conformation and the binding of PP(i), Mg(2+)(B), and Mg(2+)(C) to monomer D in a predominantly closed conformation. Taken together, these structures provide 12 independent "snapshots" of substrate or product complexes that suggest a possible sequence for metal ion binding and conformational changes required for catalysis.

PubMed: 18385128
DOI: 10.1074/jbc.M800659200

Experimental method

X-RAY DIFFRACTION (1.89 Å)