1q9d: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1q9d.gif|left|200px]] | [[Image:1q9d.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1q9d", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
| | --> | ||
| | {{STRUCTURE_1q9d| PDB=1q9d | SCENE= }} | ||
}} | |||
'''Fructose-1,6-bisphosphatase Complexed with a New Allosteric Site Inhibitor (I-State)''' | '''Fructose-1,6-bisphosphatase Complexed with a New Allosteric Site Inhibitor (I-State)''' | ||
| Line 28: | Line 25: | ||
[[Category: Choe, J Y.]] | [[Category: Choe, J Y.]] | ||
[[Category: Honzatko, R B.]] | [[Category: Honzatko, R B.]] | ||
[[Category: | [[Category: Bisphosphatase]] | ||
[[Category: | [[Category: Hydrolase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:01:50 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 06:01, 3 May 2008
Fructose-1,6-bisphosphatase Complexed with a New Allosteric Site Inhibitor (I-State)
OverviewOverview
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 StructureAbout this Structure
1Q9D is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
ReferenceReference
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 Sat May 3 06:01:50 2008