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| <SX load='6bf6' size='340' side='right' viewer='molstar' caption='[[6bf6]], [[Resolution|resolution]] 6.50Å' scene=''> | | <SX load='6bf6' size='340' side='right' viewer='molstar' caption='[[6bf6]], [[Resolution|resolution]] 6.50Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6bf6]] 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=6BF6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BF6 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6bf6]] 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=6BF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BF6 FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6b70|6b70]], [[6b3q|6b3q]], [[6b7y|6b7y]], [[6b7z|6b7z]]</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.5Å</td></tr> |
| <tr id='gene'><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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bf6 OCA], [https://pdbe.org/6bf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bf6 RCSB], [https://www.ebi.ac.uk/pdbsum/6bf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bf6 ProSAT]</span></td></tr> |
| <tr id='activity'><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6bf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bf6 OCA], [http://pdbe.org/6bf6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bf6 RCSB], [http://www.ebi.ac.uk/pdbsum/6bf6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bf6 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://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> | | [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;">
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| == Publication Abstract from PubMed ==
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| Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type 2 diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity. We also used cryoEM, X-ray crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby inducing selective degradation by substrate-assisted catalysis. Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Together, our studies provide a mechanism for how IDE selectively degrades amyloidogenic peptides and offers structural insights for developing IDE-based therapies.
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| Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme.,Zhang Z, Liang WG, Bailey LJ, Tan YZ, Wei H, Wang A, Farcasanu M, Woods VA, McCord LA, Lee D, Shang W, Deprez-Poulain R, Deprez B, Liu DR, Koide A, Koide S, Kossiakoff AA, Li S, Carragher B, Potter CS, Tang WJ Elife. 2018 Mar 29;7. pii: 33572. doi: 10.7554/eLife.33572. PMID:29596046<ref>PMID:29596046</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6bf6" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
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| __TOC__ | | __TOC__ |
| </SX> | | </SX> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Insulysin]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Bailey, L J]] | | [[Category: Bailey LJ]] |
| [[Category: Carragher, B]] | | [[Category: Carragher B]] |
| [[Category: Kossiakoff, A A]] | | [[Category: Kossiakoff AA]] |
| [[Category: Liang, W G]] | | [[Category: Liang WG]] |
| [[Category: Potter, S C]] | | [[Category: Potter SC]] |
| [[Category: Tan, Y Z]] | | [[Category: Tan YZ]] |
| [[Category: Tang, W J]] | | [[Category: Tang WJ]] |
| [[Category: Wei, H]] | | [[Category: Wei H]] |
| [[Category: Zhang, Z]] | | [[Category: Zhang Z]] |
| [[Category: Amyloid beta]]
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| [[Category: Hydrolase]]
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| [[Category: Ide]]
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