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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=7qac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qac OCA], [https://pdbe.org/7qac PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qac RCSB], [https://www.ebi.ac.uk/pdbsum/7qac PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qac 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=7qac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qac OCA], [https://pdbe.org/7qac PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qac RCSB], [https://www.ebi.ac.uk/pdbsum/7qac PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qac ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | + | <div style="background-color:#fffaf0;"> |
| - | [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>
| + | == Publication Abstract from PubMed == |
| - | == Function ==
| + | The polymorphism of human insulin upon pH variation was characterized via X-ray powder diffraction, employing a crystallization protocol previously established for co-crystallization with phenolic derivatives. Two distinct rhombohedral (R3) polymorphs and one cubic (I2(1)3) polymorph were identified with increasing pH, corresponding to the T(6), T(3)R(3)(f) and T(2) conformations of insulin, respectively. The structure of the cubic T(2) polymorph was determined via multi-profile stereochemically restrained Rietveld refinement at 2.7 A resolution. This constitutes the first cubic insulin structure to be determined from crystals grown in the presence of zinc ions, although no zinc binding was observed. The differences of the polycrystalline variant from other cubic insulin structures, as well as the nature of the pH-driven phase transitions, are discussed in detail. |
| - | [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.
| + | |
| | + | The T(2) structure of polycrystalline cubic human insulin.,Triandafillidis DP, Karavassili F, Spiliopoulou M, Valmas A, Athanasiadou M, Nikolaras G, Fili S, Kontou P, Bowler MW, Chasapis CT, Von Dreele RB, Fitch AN, Margiolaki I Acta Crystallogr D Struct Biol. 2023 May 1;79(Pt 5):374-386. doi: , 10.1107/S2059798323001328. Epub 2023 Apr 11. PMID:37039669<ref>PMID:37039669</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 7qac" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Structural highlights
Publication Abstract from PubMed
The polymorphism of human insulin upon pH variation was characterized via X-ray powder diffraction, employing a crystallization protocol previously established for co-crystallization with phenolic derivatives. Two distinct rhombohedral (R3) polymorphs and one cubic (I2(1)3) polymorph were identified with increasing pH, corresponding to the T(6), T(3)R(3)(f) and T(2) conformations of insulin, respectively. The structure of the cubic T(2) polymorph was determined via multi-profile stereochemically restrained Rietveld refinement at 2.7 A resolution. This constitutes the first cubic insulin structure to be determined from crystals grown in the presence of zinc ions, although no zinc binding was observed. The differences of the polycrystalline variant from other cubic insulin structures, as well as the nature of the pH-driven phase transitions, are discussed in detail.
The T(2) structure of polycrystalline cubic human insulin.,Triandafillidis DP, Karavassili F, Spiliopoulou M, Valmas A, Athanasiadou M, Nikolaras G, Fili S, Kontou P, Bowler MW, Chasapis CT, Von Dreele RB, Fitch AN, Margiolaki I Acta Crystallogr D Struct Biol. 2023 May 1;79(Pt 5):374-386. doi: , 10.1107/S2059798323001328. Epub 2023 Apr 11. PMID:37039669[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Triandafillidis DP, Karavassili F, Spiliopoulou M, Valmas A, Athanasiadou M, Nikolaras G, Fili S, Kontou P, Bowler MW, Chasapis CT, Von Dreele RB, Fitch AN, Margiolaki I. The T(2) structure of polycrystalline cubic human insulin. Acta Crystallogr D Struct Biol. 2023 May 1;79(Pt 5):374-386. PMID:37039669 doi:10.1107/S2059798323001328
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