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| ==Human insulin in complex with the human insulin microreceptor in turn in complex with Fv 83-7== | | ==n/a== |
| <StructureSection load='6vep' size='340' side='right'caption='[[6vep]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='6vep' size='340' side='right'caption='[[6vep]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6vep]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VEP FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VEP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VEP 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]] 2.9Å</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction</td></tr> |
| <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6vep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vep OCA], [https://pdbe.org/6vep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vep RCSB], [https://www.ebi.ac.uk/pdbsum/6vep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vep ProSAT]</span></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=6vep FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vep OCA], [https://pdbe.org/6vep PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vep RCSB], [https://www.ebi.ac.uk/pdbsum/6vep PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vep ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease ==
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| [https://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[https://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:[https://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:[https://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:[https://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 ==
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| [https://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.
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Human insulin and its current therapeutic analogs all show propensity, albeit varyingly, to self-associate into dimers and hexamers, which delays their onset of action and makes blood glucose management difficult for people with diabetes. Recently, we described a monomeric, insulin-like peptide in cone-snail venom with moderate human insulin-like bioactivity. Here, with insights from structural biology studies, we report the development of mini-Ins-a human des-octapeptide insulin analog-as a structurally minimal, full-potency insulin. Mini-Ins is monomeric and, despite the lack of the canonical B-chain C-terminal octapeptide, has similar receptor binding affinity to human insulin. Four mutations compensate for the lack of contacts normally made by the octapeptide. Mini-Ins also has similar in vitro insulin signaling and in vivo bioactivities to human insulin. The full bioactivity of mini-Ins demonstrates the dispensability of the PheB24-PheB25-TyrB26 aromatic triplet and opens a new direction for therapeutic insulin development.
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| A structurally minimized yet fully active insulin based on cone-snail venom insulin principles.,Xiong X, Menting JG, Disotuar MM, Smith NA, Delaine CA, Ghabash G, Agrawal R, Wang X, He X, Fisher SJ, MacRaild CA, Norton RS, Gajewiak J, Forbes BE, Smith BJ, Safavi-Hemami H, Olivera B, Lawrence MC, Chou DH Nat Struct Mol Biol. 2020 Jun 1. pii: 10.1038/s41594-020-0430-8. doi:, 10.1038/s41594-020-0430-8. PMID:32483339<ref>PMID:32483339</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 6vep" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Insulin 3D Structures|Insulin 3D Structures]] | | *[[Insulin 3D Structures|Insulin 3D Structures]] |
| *[[Insulin receptor 3D structures|Insulin receptor 3D structures]] | | *[[Insulin receptor 3D structures|Insulin receptor 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Mus musculus]] | | [[Category: N/a]] |
| [[Category: Lawrence MC]]
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| [[Category: Menting JGT]]
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