1q9d
From Proteopedia
(New page: 200px<br /><applet load="1q9d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q9d, resolution 2.35Å" /> '''Fructose-1,6-bisphos...) |
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| - | [[Image:1q9d.gif|left|200px]]<br /><applet load="1q9d" size=" | + | [[Image:1q9d.gif|left|200px]]<br /><applet load="1q9d" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1q9d, resolution 2.35Å" /> | caption="1q9d, resolution 2.35Å" /> | ||
'''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 | + | 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:// | + | 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== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
| - | [[Category: Choe, J | + | [[Category: Choe, J Y.]] |
| - | [[Category: Honzatko, R | + | [[Category: Honzatko, R B.]] |
[[Category: F6P]] | [[Category: F6P]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''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
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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
Categories: Fructose-bisphosphatase | Single protein | Sus scrofa | Choe, J Y. | Honzatko, R B. | F6P | MG | OI1 | PO4 | Bisphosphatase | Hydrolase
