View source for 7ezr


==Indole-2-carboxylic acid derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase==
<StructureSection load='7ezr' size='340' side='right'caption='[[7ezr]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ezr]] 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=7EZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EZR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.27&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0H1:5-ethyl-7-nitro-3-[3-oxidanylidene-3-(thiophen-2-ylsulfonylamino)propyl]-1H-indole-2-carboxylic+acid'>0H1</scene>, <scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</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=7ezr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ezr OCA], [https://pdbe.org/7ezr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ezr RCSB], [https://www.ebi.ac.uk/pdbsum/7ezr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ezr 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] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Liver fructose-1,6-bisphosphatase (FBPase) is a key enzyme in the gluconeogenesis, and its inhibitors are expected to be novel antidiabetic agents. Herein, a series of new indole and benzofuran analogues were designed and synthesized to evaluate the inhibitory activity against FBPase. As a result, the novel FBPase inhibitors bearing N-acylsulfonamide moiety on the 3-position of the indole-2-carboxylic acid scaffold (compounds 22f and 22g) were identified with IC(50)s at the submicromolar levels. Three X-ray crystal structures of the complexes were solved and revealed the structural basis for the inhibitory activity. The chemoinformatics analysis further disclosed the distinct binding features of this class of inhibitors, providing an insight for further modifications to create structurally distinct FBPase inhibitors with high potency and drug-like properties.

Discovery of Novel Indole Derivatives as Fructose-1,6-bisphosphatase Inhibitors and X-ray Cocrystal Structures Analysis.,Wang X, Zhao R, Ji W, Zhou J, Liu Q, Zhao L, Shen Z, Liu S, Xu B ACS Med Chem Lett. 2021 Dec 20;13(1):118-127. doi: , 10.1021/acsmedchemlett.1c00613. eCollection 2022 Jan 13. PMID:35059131<ref>PMID:35059131</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ezr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wang XY]]
[[Category: Xu BL]]
[[Category: Zhou J]]