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[[Image:2fix.gif|left|200px]]


{{Structure
==Structure of human liver FBPase complexed with potent benzoxazole allosteric inhibitiors==
|PDB= 2fix |SIZE=350|CAPTION= <scene name='initialview01'>2fix</scene>, resolution 3.50&Aring;
<StructureSection load='2fix' size='340' side='right'caption='[[2fix]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=870:N-[7-(3-AMINOPHENYL)-5-METHOXY-1,3-BENZOXAZOL-2-YL]-2,5-DICHLOROBENZENESULFONAMIDE'>870</scene>
<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>
|ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
|GENE=  
<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>
|DOMAIN=
<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>
|RELATEDENTRY=[[2fhy|2fhy]], [[2fie|2fie]]
</table>
|RESOURCES=<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://www.ebi.ac.uk/pdbsum/2fix PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fix RCSB]</span>
== 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 ==
[[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/fi/2fix_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=2fix ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


'''Structure of human liver FBPase complexed with potent benzoxazole allosteric inhibitiors'''
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<ref>PMID:16446092</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2fix" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]]
 
== References ==
==About this Structure==
<references/>
2FIX is a [[Single protein]] structure of 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=2FIX OCA].
__TOC__
 
</StructureSection>
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/16446092 16446092]
[[Category: Fructose-bisphosphatase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Abad-Zapatero, C.]]
[[Category: Abad-Zapatero C]]
[[Category: allosteric inhibitors human liver fbpase]]
[[Category: benzoxazole]]
[[Category: intersubunit allosteric inhibitors of human liver fbpase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:03:22 2008''

Latest revision as of 12:27, 30 August 2023

Structure of human liver FBPase complexed with potent benzoxazole allosteric inhibitiorsStructure of human liver FBPase complexed with potent benzoxazole allosteric inhibitiors

Structural highlights

2fix is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.5Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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

2fix, resolution 3.50Å

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