1Q9D

Fructose-1,6-bisphosphatase Complexed with a New Allosteric Site Inhibitor (I-State)

1Q9D の概要

• エントリーDOI: 10.2210/pdb1q9d/pdb
• 分子名称: Fructose-1,6-bisphosphatase, 6-O-phosphono-beta-D-fructofuranose, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: bisphosphatase, hydrolase
• 由来する生物種: Sus scrofa (pig)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75463.06

構造登録者

Honzatko, R.B.,Choe, J.Y. (登録日: 2003-08-25, 公開日: 2003-12-02, 最終更新日: 2023-10-25)

主引用文献

Choe, J.Y.,Nelson, S.W.,Arienti, K.L.,Axe, F.U.,Collins, T.L.,Jones, T.K.,Kimmich, R.D.,Newman, M.J.,Norvell, K.,Ripka, W.C.,Romano, S.J.,Short, K.M.,Slee, D.H.,Fromm, H.J.,Honzatko, R.B.
Inhibition of fructose-1,6-bisphosphatase by a new class of allosteric effectors
J.Biol.Chem., 278:51176-51183, 2003

PubMed Abstract: A highly constrained pseudo-tetrapeptide (OC252-324) further defines a new allosteric binding site located near the center of fructose-1,6-bisphosphatase. In a crystal structure, pairs of inhibitory molecules bind to opposite faces of the enzyme tetramer. Each ligand molecule is in contact with three of four subunits of the tetramer, hydrogen bonding with the side chain of Asp187 and the backbone carbonyl of residue 71, and electrostatically interacting with the backbone carbonyl of residue 51. The ligated complex adopts a quaternary structure between the canonical R- and T-states of fructose-1,6-bisphosphatase, and yet a dynamic loop essential for catalysis (residues 52-72) is in a conformation identical to that of the T-state enzyme. Inhibition by the pseudo-tetrapeptide is cooperative (Hill coefficient of 2), synergistic with both AMP and fructose 2,6-bisphosphate, noncompetitive with respect to Mg2+, and uncompetitive with respect to fructose 1,6-bisphosphate. The ligand dramatically lowers the concentration at which substrate inhibition dominates the kinetics of fructose-1,6-bisphosphatase. Elevated substrate concentrations employed in kinetic screens may have facilitated the discovery of this uncompetitive inhibitor. Moreover, the inhibitor could mimic an unknown natural effector of fructose-1,6-bisphosphatase, as it interacts strongly with a conserved residue of undetermined functional significance.

PubMed: 14530289
DOI: 10.1074/jbc.M308396200

実験手法

X-RAY DIFFRACTION (2.35 Å)