2vt5

From Proteopedia

(Difference between revisions)

Revision as of 11:45, 30 March 2022

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

Structural highlights

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

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

Human 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.

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
↑ Hebeisen P, Kuhn B, Kohler P, Gubler M, Huber W, Kitas E, Schott B, Benz J, Joseph C, Ruf A. Allosteric FBPase inhibitors gain 10(5) times in potency when simultaneously binding two neighboring AMP sites. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4708-12. Epub 2008 Jul 5. PMID:18650089 doi:10.1016/j.bmcl.2008.06.103

1 Structural highlights
2 Disease
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vt5"

@@ Line 3: / Line 3: @@
 <StructureSection load='2vt5' size='340' side='right'caption='[[2vt5]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2vt5]] is a 8 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=2VT5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2VT5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2vt5]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fta|1fta]], [[2jjk|2jjk]], [[2fie|2fie]], [[2fix|2fix]], [[2fhy|2fhy]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fta|1fta]], [[2jjk|2jjk]], [[2fie|2fie]], [[2fix|2fix]], [[2fhy|2fhy]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Fructose-bisphosphatase Fructose-bisphosphatase], with EC number [https://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'>[http://proteopedia.org/fgij/fg.htm?mol=2vt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vt5 OCA], [http://pdbe.org/2vt5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vt5 RCSB], [http://www.ebi.ac.uk/pdbsum/2vt5 PDBsum], [http://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'>[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>
 </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>
+[[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

2vt5

From Proteopedia

Revision as of 11:45, 30 March 2022

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

Structural highlights

Disease

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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