1q9d

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spinqualitylabelsall models 1q9d, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Overview

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.

About this Structure

1Q9D is a Single protein structure of sequence from Sus scrofa with F6P, MG, PO4 and OI1 as ligands. Active as Fructose-bisphosphatase, with EC number 3.1.3.11 Full crystallographic information is available from OCA.

Reference

Inhibition of fructose-1,6-bisphosphatase by a new class of allosteric effectors., Choe JY, Nelson SW, Arienti KL, Axe FU, Collins TL, Jones TK, Kimmich RD, Newman MJ, Norvell K, Ripka WC, Romano SJ, Short KM, Slee DH, Fromm HJ, Honzatko RB, J Biol Chem. 2003 Dec 19;278(51):51176-83. Epub 2003 Oct 6. PMID:14530289

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