2F3B

Mechanism of displacement of a catalytically essential loop from the active site of fructose-1,6-bisphosphatase

2F3B の概要

• エントリーDOI: 10.2210/pdb2f3b/pdb
• 関連するPDBエントリー: 1CNQ 1EYI 1Q9D 1YXI 1YYZ 1YZO 2F3D 2F3H
• 分子名称: Fructose-1,6-bisphosphatase 1, 6-O-phosphono-beta-D-fructofuranose, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: allostery, allosteric regulation, loop diengagement, enzyme catalysis, fbpase, fructose-1, 6-bisphosphatase, hydrolase
• 由来する生物種: Sus scrofa (pig)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37470.64

構造登録者

Iancu, C.V.,Mukund, S.,Choe, J.-Y.,Fromm, H.J.,Honzatko, R.B. (登録日: 2005-11-20, 公開日: 2006-04-25, 最終更新日: 2024-02-14)

主引用文献

Gao, Y.,Iancu, C.V.,Mukind, S.,Choe, J.Y.,Honzatko, R.B.
Mechanism of displacement of a catalytically essential loop from the active site of mammalian fructose-1,6-bisphosphatase.
Biochemistry, 52:5206-5216, 2013

PubMed Abstract: AMP triggers a 15° subunit-pair rotation in fructose-1,6-bisphosphatase (FBPase) from its active R state to its inactive T state. During this transition, a catalytically essential loop (residues 50-72) leaves its active (engaged) conformation. Here, the structures of Ile(10) → Asp FBPase and molecular dynamic simulations reveal factors responsible for loop displacement. The AMP/Mg(2+) and AMP/Zn(2+) complexes of Asp(10) FBPase are in intermediate quaternary conformations (completing 12° of the subunit-pair rotation), but the complex with Zn(2+) provides the first instance of an engaged loop in a near-T quaternary state. The 12° subunit-pair rotation generates close contacts involving the hinges (residues 50-57) and hairpin turns (residues 58-72) of the engaged loops. Additional subunit-pair rotation toward the T state would make such contacts unfavorable, presumably causing displacement of the loop. Targeted molecular dynamics simulations reveal no steric barriers to subunit-pair rotations of up to 14° followed by the displacement of the loop from the active site. Principal component analysis reveals high-amplitude motions that exacerbate steric clashes of engaged loops in the near-T state. The results of the simulations and crystal structures are in agreement: subunit-pair rotations just short of the canonical T state coupled with high-amplitude modes sterically displace the dynamic loop from the active site.

PubMed: 23844654
DOI: 10.1021/bi400532n

実験手法

X-RAY DIFFRACTION (1.8 Å)