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...)
Current revision (07:23, 25 October 2023) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1q9d.gif|left|200px]]<br /><applet load="1q9d" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1q9d, resolution 2.35&Aring;" />
 
-
'''Fructose-1,6-bisphosphatase Complexed with a New Allosteric Site Inhibitor (I-State)'''<br />
 
-
==Overview==
+
==Fructose-1,6-bisphosphatase Complexed with a New Allosteric Site Inhibitor (I-State)==
-
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.
+
<StructureSection load='1q9d' size='340' side='right'caption='[[1q9d]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1q9d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q9D FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F6P:FRUCTOSE-6-PHOSPHATE'>F6P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OI1:3-(4-HYDROXYBENZYL)-2-[1-({[2-(4-HYDROXYPHENYL)ETHYL]AMINO}CARBONYL)BUTYL]-4-OXO-3,6,11,11A-TETRAHYDRO-4H-PYRAZINO[1,2-B]ISOQUINOLIN-2-IUM-1-OLATE'>OI1</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q9d OCA], [https://pdbe.org/1q9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q9d RCSB], [https://www.ebi.ac.uk/pdbsum/1q9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q9d ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/F16P1_PIG F16P1_PIG]
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q9/1q9d_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1q9d ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
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==
+
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<ref>PMID:14530289</ref>
-
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].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14530289 14530289]
+
</div>
-
[[Category: Fructose-bisphosphatase]]
+
<div class="pdbe-citations 1q9d" style="background-color:#fffaf0;"></div>
-
[[Category: Single protein]]
+
-
[[Category: Sus scrofa]]
+
-
[[Category: Choe, J.Y.]]
+
-
[[Category: Honzatko, R.B.]]
+
-
[[Category: F6P]]
+
-
[[Category: MG]]
+
-
[[Category: OI1]]
+
-
[[Category: PO4]]
+
-
[[Category: bisphosphatase]]
+
-
[[Category: hydrolase]]
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:30:21 2007''
+
==See Also==
 +
*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
 +
[[Category: Sus scrofa]]
 +
[[Category: Choe JY]]
 +
[[Category: Honzatko RB]]

Current revision

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

PDB ID 1q9d

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools