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{{STRUCTURE_2wbd|  PDB=2wbd  |  SCENE=  }}
==FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE-1-PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH AN AMP SITE INHIBITOR==
===FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE-1-PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH AN AMP SITE INHIBITOR===
<StructureSection load='2wbd' size='340' side='right' caption='[[2wbd]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
{{ABSTRACT_PUBMED_19969452}}
== Structural highlights ==
<table><tr><td colspan='2'>[[2wbd]] 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=2WBD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WBD FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RO5:N-[(5-BROMO-1,3-THIAZOL-2-YL)CARBAMOYL]-3-ETHYLBENZENESULFONAMIDE'>RO5</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fta|1fta]], [[2jjk|2jjk]], [[2vt5|2vt5]], [[2fie|2fie]], [[2wbb|2wbb]], [[2fhy|2fhy]], [[2fix|2fix]]</td></tr>
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wbd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wbd RCSB], [http://www.ebi.ac.uk/pdbsum/2wbd PDBsum]</span></td></tr>
<table>
== 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> 
== Function ==


==Disease==
== Evolutionary Conservation ==
[[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>
[[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/wb/2wbd_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sulfonylureido thiazoles were identified from a HTS campaign and optimized through a combination of structure-activity studies, X-ray crystallography and molecular modeling to yield potent inhibitors of fructose-1,6-bisphosphatase. Compound 12 showed favorable ADME properties, for example, F=70%, and a robust 32% glucose reduction in the acute db/db mouse model for Type-2 diabetes.


==About this Structure==
Sulfonylureido thiazoles as fructose-1,6-bisphosphatase inhibitors for the treatment of type-2 diabetes.,Kitas E, Mohr P, Kuhn B, Hebeisen P, Wessel HP, Haap W, Ruf A, Benz J, Joseph C, Huber W, Sanchez RA, Paehler A, Benardeau A, Gubler M, Schott B, Tozzo E Bioorg Med Chem Lett. 2010 Jan 15;20(2):594-9. Epub 2009 Nov 22. PMID:19969452<ref>PMID:19969452</ref>
[[2wbd]] 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=2WBD OCA].
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Fructose-1%2C6-bisphosphatase|Fructose-1%2C6-bisphosphatase]]
*[[Fructose-1%2C6-bisphosphatase|Fructose-1%2C6-bisphosphatase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:019969452</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Fructose-bisphosphatase]]
[[Category: Fructose-bisphosphatase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]

Revision as of 04:14, 1 October 2014

FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE-1-PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH AN AMP SITE INHIBITORFRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE-1-PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH AN AMP SITE INHIBITOR

Structural highlights

2wbd is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:1fta, 2jjk, 2vt5, 2fie, 2wbb, 2fhy, 2fix
Activity:Fructose-bisphosphatase, with EC number 3.1.3.11
Resources:FirstGlance, OCA, RCSB, PDBsum

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

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

Sulfonylureido thiazoles were identified from a HTS campaign and optimized through a combination of structure-activity studies, X-ray crystallography and molecular modeling to yield potent inhibitors of fructose-1,6-bisphosphatase. Compound 12 showed favorable ADME properties, for example, F=70%, and a robust 32% glucose reduction in the acute db/db mouse model for Type-2 diabetes.

Sulfonylureido thiazoles as fructose-1,6-bisphosphatase inhibitors for the treatment of type-2 diabetes.,Kitas E, Mohr P, Kuhn B, Hebeisen P, Wessel HP, Haap W, Ruf A, Benz J, Joseph C, Huber W, Sanchez RA, Paehler A, Benardeau A, Gubler M, Schott B, Tozzo E Bioorg Med Chem Lett. 2010 Jan 15;20(2):594-9. Epub 2009 Nov 22. PMID:19969452[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. ↑ Kitas E, Mohr P, Kuhn B, Hebeisen P, Wessel HP, Haap W, Ruf A, Benz J, Joseph C, Huber W, Sanchez RA, Paehler A, Benardeau A, Gubler M, Schott B, Tozzo E. Sulfonylureido thiazoles as fructose-1,6-bisphosphatase inhibitors for the treatment of type-2 diabetes. Bioorg Med Chem Lett. 2010 Jan 15;20(2):594-9. Epub 2009 Nov 22. PMID:19969452 doi:10.1016/j.bmcl.2009.11.093

2wbd, resolution 2.40Å

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