6lw2: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
(One intermediate revision by the same user not shown)
Line 3: Line 3:
<StructureSection load='6lw2' size='340' side='right'caption='[[6lw2]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
<StructureSection load='6lw2' size='340' side='right'caption='[[6lw2]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6lw2]] is a 4 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=6LW2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LW2 FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LW2 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EW0:7-chloranyl-4-[(3-methoxyphenyl)amino]-N-(4-methoxyphenyl)sulfonyl-1-methyl-indole-2-carboxamide'>EW0</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]] 2.4&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FBP1, FBP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EW0:7-chloranyl-4-[(3-methoxyphenyl)amino]-N-(4-methoxyphenyl)sulfonyl-1-methyl-indole-2-carboxamide'>EW0</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6lw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lw2 OCA], [https://pdbe.org/6lw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lw2 RCSB], [https://www.ebi.ac.uk/pdbsum/6lw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lw2 ProSAT]</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=6lw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lw2 OCA], [http://pdbe.org/6lw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lw2 RCSB], [http://www.ebi.ac.uk/pdbsum/6lw2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lw2 ProSAT]</span></td></tr>
</table>
</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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Liver fructose-1,6-bisphosphatase (FBPase) is a key enzyme in the gluconeogenesis pathway. Inhibiting FBPase activity represents a potential treatment for type 2 diabetes mellitus. A series of novel N-arylsulfonyl-4-arylamino-indole-2-carboxamide derivatives have been disclosed as FBPase inhibitors. Through extensive structure-activity relationship investigations, a promising candidate molecule Cpd118 [sodium (7-chloro-4-((3-methoxyphenyl)amino)-1-methyl-1H-indole-2-carbonyl] [(4-methoxyphenyl)sulfonyl)amide] has been identified with high inhibitory activity against human liver FBPase (IC50, 0.029 +/- 0.006 muM) and high selectivity relative to the other six AMP-binding enzymes. Importantly, Cpd118 produced significant glucose-lowering effects on both type 2 diabetic KKAy mice and ZDF rats as demonstrated by substantial reductions in the fasting and postprandial blood glucose levels, as well as the HbA1c level. Furthermore, Cpd118 elicited a favorable pharmacokinetic profile with an oral bioavailability of 99.1%. Moreover, the X-ray crystal structure of the Cpd118-FBPase complex was resolved, which revealed a unique binding mode and provided a structural basis for its high potency and selectivity.
Discovery of N-Arylsulfonyl-Indole-2-Carboxamide Derivatives as Potent, Selective, and Orally Bioavailable Fructose-1,6-Bisphosphatase Inhibitors-Design, Synthesis, In Vivo Glucose Lowering Effects, and X-ray Crystal Complex Analysis.,Zhou J, Bie J, Wang X, Liu Q, Li R, Chen H, Hu J, Cao H, Ji W, Li Y, Liu S, Shen Z, Xu B J Med Chem. 2020 Sep 24;63(18):10307-10329. doi: 10.1021/acs.jmedchem.0c00726., Epub 2020 Sep 12. PMID:32820629<ref>PMID:32820629</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6lw2" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]]
*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Fructose-bisphosphatase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Wang, X Y]]
[[Category: Wang XY]]
[[Category: Xu, B L]]
[[Category: Xu BL]]
[[Category: Zhou, J]]
[[Category: Zhou J]]
[[Category: Fbpase]]
[[Category: Hydrolase]]
[[Category: N-arylsulfonyl-indole-2-carboxamide]]
Retrieved from "https://proteopedia.org/6lw2"