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| | <StructureSection load='2fix' size='340' side='right'caption='[[2fix]], [[Resolution|resolution]] 3.50Å' scene=''> | | <StructureSection load='2fix' size='340' side='right'caption='[[2fix]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2fix]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FIX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FIX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2fix]] is a 4 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=2FIX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FIX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=870:N-[7-(3-AMINOPHENYL)-5-METHOXY-1,3-BENZOXAZOL-2-YL]-2,5-DICHLOROBENZENESULFONAMIDE'>870</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]] 3.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fhy|2fhy]], [[2fie|2fie]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=870:N-[7-(3-AMINOPHENYL)-5-METHOXY-1,3-BENZOXAZOL-2-YL]-2,5-DICHLOROBENZENESULFONAMIDE'>870</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=2fix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fix OCA], [https://pdbe.org/2fix PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fix RCSB], [https://www.ebi.ac.uk/pdbsum/2fix PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fix 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=2fix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fix OCA], [http://pdbe.org/2fix PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fix RCSB], [http://www.ebi.ac.uk/pdbsum/2fix PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2fix ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [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 == |
| | + | [https://www.uniprot.org/uniprot/F16P1_HUMAN F16P1_HUMAN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Fructose-bisphosphatase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Abad-Zapatero, C]] | + | [[Category: Abad-Zapatero C]] |
| - | [[Category: Allosteric inhibitors human liver fbpase]]
| + | |
| - | [[Category: Benzoxazole]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Intersubunit allosteric inhibitors of human liver fbpase]]
| + | |
| 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
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
A series of novel benzoxazole benzenesulfonamides was synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase-1). Extensive SAR studies led to a potent inhibitor, 53, with an IC(50) of 0.57microM. Compound 17 exhibited excellent bioavailability and a good pharmacokinetic profile in rats.
Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase.,Lai C, Gum RJ, Daly M, Fry EH, Hutchins C, Abad-Zapatero C, von Geldern TW Bioorg Med Chem Lett. 2006 Apr 1;16(7):1807-10. Epub 2006 Jan 30. PMID:16446092[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
- ↑ Lai C, Gum RJ, Daly M, Fry EH, Hutchins C, Abad-Zapatero C, von Geldern TW. Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1807-10. Epub 2006 Jan 30. PMID:16446092 doi:10.1016/j.bmcl.2006.01.014
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