4gs8: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Structure analysis of cysteine free insulin degrading enzyme (ide) with compound bdm43079 [{[(s)-2-(1h-imidazol-4-yl)-1-methylcarbamoyl-ethylcarbamoyl]-methyl}-(3-phenyl-propyl)-amino]-acetic acid== | |||
<StructureSection load='4gs8' size='340' side='right' caption='[[4gs8]], [[Resolution|resolution]] 2.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4gs8]] is a 2 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=4GS8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GS8 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MGJ:N-(CARBOXYMETHYL)-N-(3-PHENYLPROPYL)GLYCYL-N-METHYL-L-HISTIDINAMIDE'>MGJ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gsc|4gsc]], [[4gse|4gse]], [[4gsf|4gsf]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IDE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gs8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gs8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gs8 RCSB], [http://www.ebi.ac.uk/pdbsum/4gs8 PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Insulin degrading enzyme (IDE) is a highly conserved zinc metalloprotease that is involved in the clearance of various physiologically peptides like amyloid-beta and insulin. This enzyme has been involved in the physiopathology of diabetes and Alzheimer's disease. We describe here a series of small molecules discovered by screening. Co-crystallization of the compounds with IDE revealed a binding both at the permanent exosite and at the discontinuous, conformational catalytic site. Preliminary structure-activity relationships are described. Selective inhibition of amyloid-beta degradation over insulin hydrolysis was possible. Neuroblastoma cells treated with the optimized compound display a dose-dependent increase in amyloid-beta levels. | |||
Imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, substrate-dependent modulators of insulin-degrading enzyme in amyloid-beta hydrolysis.,Charton J, Gauriot M, Guo Q, Hennuyer N, Marechal X, Dumont J, Hamdane M, Pottiez V, Landry V, Sperandio O, Flipo M, Buee L, Staels B, Leroux F, Tang WJ, Deprez B, Deprez-Poulain R Eur J Med Chem. 2014 Apr 4;79C:184-193. doi: 10.1016/j.ejmech.2014.04.009. PMID:24735644<ref>PMID:24735644</ref> | |||
[ | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
<references | |||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Insulysin]] | [[Category: Insulysin]] | ||
Revision as of 10:11, 28 May 2014
Structure analysis of cysteine free insulin degrading enzyme (ide) with compound bdm43079 [{[(s)-2-(1h-imidazol-4-yl)-1-methylcarbamoyl-ethylcarbamoyl]-methyl}-(3-phenyl-propyl)-amino]-acetic acidStructure analysis of cysteine free insulin degrading enzyme (ide) with compound bdm43079 [{[(s)-2-(1h-imidazol-4-yl)-1-methylcarbamoyl-ethylcarbamoyl]-methyl}-(3-phenyl-propyl)-amino]-acetic acid
Structural highlights
Publication Abstract from PubMedInsulin degrading enzyme (IDE) is a highly conserved zinc metalloprotease that is involved in the clearance of various physiologically peptides like amyloid-beta and insulin. This enzyme has been involved in the physiopathology of diabetes and Alzheimer's disease. We describe here a series of small molecules discovered by screening. Co-crystallization of the compounds with IDE revealed a binding both at the permanent exosite and at the discontinuous, conformational catalytic site. Preliminary structure-activity relationships are described. Selective inhibition of amyloid-beta degradation over insulin hydrolysis was possible. Neuroblastoma cells treated with the optimized compound display a dose-dependent increase in amyloid-beta levels. Imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, substrate-dependent modulators of insulin-degrading enzyme in amyloid-beta hydrolysis.,Charton J, Gauriot M, Guo Q, Hennuyer N, Marechal X, Dumont J, Hamdane M, Pottiez V, Landry V, Sperandio O, Flipo M, Buee L, Staels B, Leroux F, Tang WJ, Deprez B, Deprez-Poulain R Eur J Med Chem. 2014 Apr 4;79C:184-193. doi: 10.1016/j.ejmech.2014.04.009. PMID:24735644[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||||