1q9d

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="1q9d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q9d, resolution 2.35&Aring;" /> '''Fructose-1,6-bisphos...)
Line 1: Line 1:
-
[[Image:1q9d.gif|left|200px]]<br /><applet load="1q9d" size="450" color="white" frame="true" align="right" spinBox="true"
+
[[Image:1q9d.gif|left|200px]]<br /><applet load="1q9d" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1q9d, resolution 2.35&Aring;" />
caption="1q9d, resolution 2.35&Aring;" />
'''Fructose-1,6-bisphosphatase Complexed with a New Allosteric Site Inhibitor (I-State)'''<br />
'''Fructose-1,6-bisphosphatase Complexed with a New Allosteric Site Inhibitor (I-State)'''<br />
==Overview==
==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.
+
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==
==About this Structure==
-
1Q9D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with F6P, MG, PO4 and OI1 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphatase Fructose-bisphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.11 3.1.3.11] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Q9D OCA].
+
1Q9D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=F6P:'>F6P</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=OI1:'>OI1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphatase Fructose-bisphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.11 3.1.3.11] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q9D OCA].
==Reference==
==Reference==
Line 14: Line 14:
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
-
[[Category: Choe, J.Y.]]
+
[[Category: Choe, J Y.]]
-
[[Category: Honzatko, R.B.]]
+
[[Category: Honzatko, R B.]]
[[Category: F6P]]
[[Category: F6P]]
[[Category: MG]]
[[Category: MG]]
Line 23: Line 23:
[[Category: hydrolase]]
[[Category: hydrolase]]
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:30:21 2007''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:37:15 2008''

Revision as of 12:37, 21 February 2008


1q9d, resolution 2.35Å

Drag the structure with the mouse to rotate

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 , , and 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

Page seeded by OCA on Thu Feb 21 14:37:15 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools