1his
From Proteopedia
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| - | + | ==Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis.== | |
| - | + | <StructureSection load='1his' size='340' side='right' caption='[[1his]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[1his]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HIS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HIS FirstGlance]. <br> | ||
| + | </td></tr><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=1his FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1his OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1his RCSB], [http://www.ebi.ac.uk/pdbsum/1his PDBsum]</span></td></tr> | ||
| + | </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> | ||
| + | == Function == | ||
| + | [[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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Structures of insulin in different crystal forms exhibit significant local and nonlocal differences, including correlated displacement of elements of secondary structure. Here we describe the solution structure and dynamics of a monomeric insulin analogue, des-pentapeptide-(B26-B30)-insulin (DPI), as determined by two-dimensional NMR spectroscopy and distance geometry/restrained molecular dynamics (DG/RMD). Although the solution structure of DPI exhibits a general similarity to its crystal structure, individual DG/RMD structures in the NMR ensemble differ by rigid-body displacements of alpha-helices that span the range of different crystal forms. These results suggest that DPI exists as a partially folded state formed by coalescence of distinct alpha-helix-associated microdomains. The physical reality of this model is investigated by comparison of the observed two-dimensional nuclear Overhauser enhancement (NOE) spectroscopy (NOESY) spectrum with that predicted from crystal and DG/RMD structures. The observed NOESY spectrum contains fewer tertiary contacts than predicted by any single simulation, but it matches their shared features; such "ensemble correspondence" is likely to reflect the effect of protein dynamics on observed NOE intensities. We propose (i) that the folded state of DPI is analogous to that of a compact protein-folding intermediate rather than a conventional native state and (ii) that the molten state is the biologically active species. This proposal (the molten-globule hypothesis) leads to testable thermodynamic predictions and has general implications for protein design. | ||
| - | + | Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis.,Hua QX, Kochoyan M, Weiss MA Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2379-83. PMID:1549601<ref>PMID:1549601</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Molecular Playground/Insulin|Molecular Playground/Insulin]] | *[[Molecular Playground/Insulin|Molecular Playground/Insulin]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Hua, Q X | + | [[Category: Hua, Q X]] |
| - | [[Category: Kochoyan, M | + | [[Category: Kochoyan, M]] |
| - | [[Category: Weiss, M A | + | [[Category: Weiss, M A]] |
[[Category: Hormone]] | [[Category: Hormone]] | ||
Revision as of 12:13, 18 December 2014
Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis.
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