2fie: Difference between revisions

Latest revision as of 09:27, 30 August 2023

Structure of human liver FBPase complexed with potent benzoxazole allosteric inhibitors

Structural highlights

2fie 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 2.81Å
Ligands:	A74
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.

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[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

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <StructureSection load='2fie' size='340' side='right'caption='[[2fie]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2fie]] is a 4 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=2FIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FIE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2fie]] 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=2FIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FIE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A74:2,5-DICHLORO-N-[5-METHOXY-7-(6-METHOXYPYRIDIN-3-YL)-1,3-BENZOXAZOL-2-YL]BENZENESULFONAMIDE'>A74</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]] 2.81&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2fhy|2fhy]], [[2fix|2fix]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A74:2,5-DICHLORO-N-[5-METHOXY-7-(6-METHOXYPYRIDIN-3-YL)-1,3-BENZOXAZOL-2-YL]BENZENESULFONAMIDE'>A74</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=2fie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fie OCA], [https://pdbe.org/2fie PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fie RCSB], [https://www.ebi.ac.uk/pdbsum/2fie PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fie ProSAT]</span></td></tr>
 </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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Fructose-bisphosphatase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[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]]

2fie: Difference between revisions

Latest revision as of 09:27, 30 August 2023

Structure of human liver FBPase complexed with potent benzoxazole allosteric inhibitors

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools