3CKE

Crystal structure of aristolochene synthase in complex with 12,13-difluorofarnesyl diphosphate

3CKE の概要

• エントリーDOI: 10.2210/pdb3cke/pdb
• 関連するPDBエントリー: 3BNX 3BNY
• 分子名称: Aristolochene synthase, CHLORIDE ION, (2E,6E)-12-fluoro-11-(fluoromethyl)-3,7-dimethyldodeca-2,6,10-trien-1-yl trihydrogen diphosphate, ... (8 entities in total)
• 機能のキーワード: substrate binding, metal ion binding, catalysis, conformational changes, lyase
• 由来する生物種: Aspergillus terreus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 147858.16

構造登録者

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. (登録日: 2008-03-14, 公開日: 2008-04-01, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)