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3qz2

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==The structure of cysteine-free human insulin degrading enzyme==
==The structure of cysteine-free human insulin degrading enzyme==
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<StructureSection load='3qz2' size='340' side='right' caption='[[3qz2]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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<StructureSection load='3qz2' size='340' side='right'caption='[[3qz2]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3qz2]] 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=3QZ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QZ2 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3qz2]] is a 2 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=3QZ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QZ2 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<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=3qz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qz2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qz2 RCSB], [http://www.ebi.ac.uk/pdbsum/3qz2 PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qz2 OCA], [https://pdbe.org/3qz2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qz2 RCSB], [https://www.ebi.ac.uk/pdbsum/3qz2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qz2 ProSAT]</span></td></tr>
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<table>
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</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[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>
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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.
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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>
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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</div>
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*[[Insulin-degrading enzyme 3D structures|Insulin-degrading enzyme 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Insulysin]]
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[[Category: Large Structures]]
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[[Category: Guo, Q.]]
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[[Category: Guo Q]]
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[[Category: Tang, W J.]]
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[[Category: Tang WJ]]
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[[Category: Hydrolase]]
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[[Category: Insulin degrading enzyme]]
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Current revision

The structure of cysteine-free human insulin degrading enzyme

PDB ID 3qz2

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