2vt5: Difference between revisions
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==FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE -1-PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH A DUAL BINDING AMP SITE INHIBITOR== | |||
<StructureSection load='2vt5' size='340' side='right' caption='[[2vt5]], [[Resolution|resolution]] 2.20Å' scene=''> | ==FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE -1- PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH A DUAL BINDING AMP SITE INHIBITOR== | ||
<StructureSection load='2vt5' size='340' side='right'caption='[[2vt5]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2vt5]] is a 8 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2vt5]] 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=2VT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VT5 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ROK:4-AMINO-N-[(2-SULFANYLETHYL)CARBAMOYL]BENZENESULFONAMIDE'>ROK</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=2vt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vt5 OCA], [https://pdbe.org/2vt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vt5 RCSB], [https://www.ebi.ac.uk/pdbsum/2vt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vt5 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == 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]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vt/2vt5_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vt/2vt5_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=2vt5 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 28: | Line 30: | ||
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 2vt5" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Fructose-1%2C6-bisphosphatase|Fructose-1%2C6-bisphosphatase]] | *[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Benz | [[Category: Large Structures]] | ||
[[Category: Fol | [[Category: Benz J]] | ||
[[Category: Joseph | [[Category: Fol B]] | ||
[[Category: Ruf | [[Category: Joseph C]] | ||
[[Category: Tetaz | [[Category: Ruf A]] | ||
[[Category: Tetaz T]] | |||
Latest revision as of 13:03, 9 May 2024
FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE -1- PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH A DUAL BINDING AMP SITE INHIBITORFRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE -1- PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH A DUAL BINDING AMP SITE INHIBITOR
Structural highlights
DiseaseF16P1_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] FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman fructose-1,6-bisphosphatase (FBPase, EC 3.1.3.11) is a key gluconeogenic enzyme, responsible for the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate, and thus presents an opportunity for the development of novel therapeutics focused on lowering the hepatic glucose production in type 2 diabetics. In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. In an HTS campaign aromatic sulfonylureas have been identified as FBPase inhibitors mimicking AMP. By bridging two adjacent allosteric binding sites using two aromatic sulfonylureas as anchor units and covalently linking them, it was possible to obtain dual binding AMP site inhibitors that exhibit a strong inhibitory effect. Allosteric FBPase inhibitors gain 10(5) times in potency when simultaneously binding two neighboring AMP sites.,Hebeisen P, Kuhn B, Kohler P, Gubler M, Huber W, Kitas E, Schott B, Benz J, Joseph C, Ruf A Bioorg Med Chem Lett. 2008 Aug 15;18(16):4708-12. Epub 2008 Jul 5. PMID:18650089[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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