2ypu: Difference between revisions
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New page: '''Unreleased structure''' The entry 2ypu is ON HOLD until Paper Publication Authors: Guo, Q., Deprez-Poulain, R., Deprez, B., Tang, W.-J. Description: human insulin degrading enzyme E... |
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==human insulin degrading enzyme E111Q in complex with inhibitor compound 41367== | |||
<StructureSection load='2ypu' size='340' side='right'caption='[[2ypu]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ypu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2yb3 2yb3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YPU 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]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I41:2-[[2-[[(2S)-3-(3H-IMIDAZOL-4-YL)-1-METHOXY-1-OXO-PROPAN-2-YL]AMINO]-2-OXO-ETHYL]-(PHENYLMETHYL)AMINO]ETHANOIC+ACID'>I41</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2ypu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ypu OCA], [https://pdbe.org/2ypu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ypu RCSB], [https://www.ebi.ac.uk/pdbsum/2ypu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ypu ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/IDE_HUMAN IDE_HUMAN] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.<ref>PMID:10684867</ref> <ref>PMID:17613531</ref> <ref>PMID:18986166</ref> | |||
<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> | |||
<div class="pdbe-citations 2ypu" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Insulin-degrading enzyme 3D structures|Insulin-degrading enzyme 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Deprez B]] | |||
[[Category: Deprez-Poulain R]] | |||
[[Category: Guo Q]] | |||
[[Category: Tang W-J]] | |||
Latest revision as of 13:57, 20 December 2023
human insulin degrading enzyme E111Q in complex with inhibitor compound 41367human insulin degrading enzyme E111Q in complex with inhibitor compound 41367
Structural highlights
FunctionIDE_HUMAN Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.[1] [2] [3] 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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