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2kqp

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{{Seed}}
 
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[[Image:2kqp.png|left|200px]]
 
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<!--
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==NMR Structure of Proinsulin==
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The line below this paragraph, containing "STRUCTURE_2kqp", creates the "Structure Box" on the page.
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<StructureSection load='2kqp' size='340' side='right'caption='[[2kqp]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2kqp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KQP FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">INS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2kqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kqp OCA], [https://pdbe.org/2kqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kqp RCSB], [https://www.ebi.ac.uk/pdbsum/2kqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kqp ProSAT]</span></td></tr>
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{{STRUCTURE_2kqp| PDB=2kqp | SCENE= }}
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</table>
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== 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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kq/2kqp_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kqp ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The folding of proinsulin, the single-chain precursor of insulin, ensures native disulfide pairing in pancreatic beta-cells. Mutations that impair folding cause neonatal diabetes mellitus. Although the classical structure of insulin is well established, proinsulin is refractory to crystallization. Here, we employ heteronuclear NMR spectroscopy to characterize a monomeric analogue. Proinsulin contains a native-like insulin moiety (A- and B-domains); the tethered connecting (C) domain (as probed by {(1)H}-(15)N nuclear Overhauser enhancements) is progressively less ordered. Although the BC junction is flexible, residues near the CA junction exhibit alpha-helical-like features. Relative to canonical alpha-helices, however, segmental (13)C(alpha/beta) chemical shifts are attenuated, suggesting that this junction and contiguous A-chain residues are molten. We propose that flexibility at each C-domain junction facilitates prohormone processing. Studies of protease SPC3 (PC1/3) suggest that C-domain sequences contribute to cleavage site selection. The structure of proinsulin provides a foundation for studies of insulin biosynthesis and its impairment in monogenic forms of diabetes mellitus.
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===NMR Structure of Proinsulin===
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Solution structure of proinsulin: connecting domain flexibility and prohormone processing.,Yang Y, Hua QX, Liu J, Shimizu EH, Choquette MH, Mackin RB, Weiss MA J Biol Chem. 2010 Mar 12;285(11):7847-51. Epub 2010 Jan 27. PMID:20106974<ref>PMID:20106974</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2kqp" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20106974}}, adds the Publication Abstract to the page
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*[[Insulin 3D Structures|Insulin 3D Structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20106974 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20106974}}
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__TOC__
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</StructureSection>
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==Disease==
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[[Category: Human]]
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Known disease associated with this structure: Hyperproinsulinemia, familial, with or without diabetes OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]]
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[[Category: Large Structures]]
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[[Category: Hua, Q X]]
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==About this Structure==
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[[Category: Mackin, R B]]
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2KQP is a 1 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=2KQP OCA].
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[[Category: Weiss, M A]]
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[[Category: Yang, Y]]
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==Reference==
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<ref group="xtra">PMID:20106974</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
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[[Category: Hua, Q X.]]
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[[Category: Mackin, R B.]]
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[[Category: Weiss, M A.]]
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[[Category: Yang, Y.]]
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[[Category: Carbohydrate metabolism]]
[[Category: Carbohydrate metabolism]]
[[Category: Cleavage on pair of basic residue]]
[[Category: Cleavage on pair of basic residue]]
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[[Category: Proinsulin]]
[[Category: Proinsulin]]
[[Category: Secreted]]
[[Category: Secreted]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 5 11:19:28 2010''
 

Current revision

NMR Structure of Proinsulin

PDB ID 2kqp

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