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| ==Cryo-EM structure of human insulin degrading enzyme in complex with insulin== | | ==Cryo-EM structure of human insulin degrading enzyme in complex with insulin== |
| <StructureSection load='6bfc' size='340' side='right' caption='[[6bfc]], [[Resolution|resolution]] 3.70Å' scene=''> | | <SX load='6bfc' size='340' side='right' viewer='molstar' caption='[[6bfc]], [[Resolution|resolution]] 3.70Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6bfc]] 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=6BFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BFC FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6bfc]] is a 4 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=6BFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BFC FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6b3q|6b3q]]</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]] 3.7Å</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]), INS ([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=6bfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bfc OCA], [https://pdbe.org/6bfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bfc RCSB], [https://www.ebi.ac.uk/pdbsum/6bfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bfc 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bfc OCA], [http://pdbe.org/6bfc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bfc RCSB], [http://www.ebi.ac.uk/pdbsum/6bfc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bfc ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Disease ==
| |
| [[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[http://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[http://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[http://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[http://omim.org/entry/613370 613370]]. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>
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| == 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> [[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. | | [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;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| </div> | | </div> |
| <div class="pdbe-citations 6bfc" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6bfc" style="background-color:#fffaf0;"></div> |
| | |
| | ==See Also== |
| | *[[Insulin 3D Structures|Insulin 3D Structures]] |
| | *[[Insulin-degrading enzyme 3D structures|Insulin-degrading enzyme 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </SX> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Insulysin]] | | [[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: Hormone]]
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| [[Category: Hydrolase-hormone complex]]
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| [[Category: Ide]]
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