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| | ==Human liver fructose-1,6-bisphosphatase(d-fructose-1,6-bisphosphate, 1-phosphohydrolase) (e.c.3.1.3.11) complexed with the allosteric inhibitor 3== | | ==Human liver fructose-1,6-bisphosphatase(d-fructose-1,6-bisphosphate, 1-phosphohydrolase) (e.c.3.1.3.11) complexed with the allosteric inhibitor 3== |
| - | <StructureSection load='4mjo' size='340' side='right' caption='[[4mjo]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='4mjo' size='340' side='right'caption='[[4mjo]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mjo]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MJO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MJO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mjo]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MJO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MJO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2C1:N-({4-BROMO-6-[(METHYLCARBAMOYL)AMINO]PYRIDIN-2-YL}CARBAMOYL)-5-(2-METHOXYETHYL)-4-METHYLTHIOPHENE-2-SULFONAMIDE'>2C1</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vt5|2vt5]], [[2jjk|2jjk]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2C1:N-({4-BROMO-6-[(METHYLCARBAMOYL)AMINO]PYRIDIN-2-YL}CARBAMOYL)-5-(2-METHOXYETHYL)-4-METHYLTHIOPHENE-2-SULFONAMIDE'>2C1</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></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=4mjo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mjo OCA], [https://pdbe.org/4mjo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mjo RCSB], [https://www.ebi.ac.uk/pdbsum/4mjo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mjo ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mjo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mjo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mjo RCSB], [http://www.ebi.ac.uk/pdbsum/4mjo PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/F16P1_HUMAN F16P1_HUMAN]] Defects in FBP1 are the cause of fructose-1,6-bisphosphatase deficiency (FBPD) [MIM:[http://omim.org/entry/229700 229700]]. FBPD is inherited as an autosomal recessive disorder mainly in the liver and causes life-threatening episodes of hypoglycemia and metabolic acidosis (lactacidemia) in newborn infants or young children.<ref>PMID:9382095</ref> <ref>PMID:12126934</ref> | + | [https://www.uniprot.org/uniprot/F16P1_HUMAN F16P1_HUMAN] Defects in FBP1 are the cause of fructose-1,6-bisphosphatase deficiency (FBPD) [MIM:[https://omim.org/entry/229700 229700]. FBPD is inherited as an autosomal recessive disorder mainly in the liver and causes life-threatening episodes of hypoglycemia and metabolic acidosis (lactacidemia) in newborn infants or young children.<ref>PMID:9382095</ref> <ref>PMID:12126934</ref> |
| | == Function == | | == Function == |
| - | | + | [https://www.uniprot.org/uniprot/F16P1_HUMAN F16P1_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4mjo" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Fructose-bisphosphatase]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Benz, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Joseph, C]] | + | [[Category: Benz J]] |
| - | [[Category: Ruf, A]] | + | [[Category: Joseph C]] |
| - | [[Category: Tetaz, T]] | + | [[Category: Ruf A]] |
| - | [[Category: Allostery]]
| + | [[Category: Tetaz T]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| Structural highlights
Disease
F16P1_HUMAN Defects in FBP1 are the cause of fructose-1,6-bisphosphatase deficiency (FBPD) [MIM:229700. FBPD is inherited as an autosomal recessive disorder mainly in the liver and causes life-threatening episodes of hypoglycemia and metabolic acidosis (lactacidemia) in newborn infants or young children.[1] [2]
Function
F16P1_HUMAN
Publication Abstract from PubMed
This study highlights the benefits of nano electrospray ionization mass spectrometry (nanoESI-MS) as a fast and label-free method not only for determination of dissociation constants (KD) of a cooperatively regulated enzyme, but also to better understand the mechanism of enzymatic cooperativity of multimeric proteins. We present an approach to investigate the allosteric mechanism in the binding of inhibitors to the homotetrameric enzyme fructose-1,6-bisphosphatase (FBPase), a potential therapeutic target for glucose control in type-2 diabetes. A series of inhibitors binding at an allosteric site of FBPase were investigated to determine their KDs by nanoESI-MS. The KDs determined by ESI-MS correlate with IC50 values in solution very well. The Hill coefficients derived from nanoESI-MS suggest positive cooperativity. From single-point measurements we could obtain information on relative potency, stoichiometry, conformational changes and mechanism of cooperativity. A new X-ray crystal structure of FBPase tetramer binding ligand 3 in a 4:4 stoichiometry is also reported. NanoESI-MS based results match the current understanding of the investigated system and are in agreement with the X-ray structural data, but provides additional mechanistic insight on the ligand binding, due to the better dynamic resolution. This method offers a powerful approach for studying other proteins with allosteric binding sites as well.
Determination of Protein-Ligand Binding Constants of a Cooperatively Regulated Tetrameric Enzyme Using Electrospray Mass Spectrometry.,Cubrilovic D, Haap W, Barylyuk K, Ruf A, Badertscher M, Gubler M, Tetaz T, Joseph C, Benz J, Zenobi R ACS Chem Biol. 2013 Oct 15. PMID:24128068[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kikawa Y, Inuzuka M, Jin BY, Kaji S, Koga J, Yamamoto Y, Fujisawa K, Hata I, Nakai A, Shigematsu Y, Mizunuma H, Taketo A, Mayumi M, Sudo M. Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency. Am J Hum Genet. 1997 Oct;61(4):852-61. PMID:9382095
- ↑ Matsuura T, Chinen Y, Arashiro R, Katsuren K, Tamura T, Hyakuna N, Ohta T. Two newly identified genomic mutations in a Japanese female patient with fructose-1,6-bisphosphatase (FBPase) deficiency. Mol Genet Metab. 2002 Jul;76(3):207-10. PMID:12126934
- ↑ Cubrilovic D, Haap W, Barylyuk K, Ruf A, Badertscher M, Gubler M, Tetaz T, Joseph C, Benz J, Zenobi R. Determination of Protein-Ligand Binding Constants of a Cooperatively Regulated Tetrameric Enzyme Using Electrospray Mass Spectrometry. ACS Chem Biol. 2013 Oct 15. PMID:24128068 doi:http://dx.doi.org/10.1021/cb4007002
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