View source for 2qiu


==Structure of Human Arg-Insulin==
<StructureSection load='2qiu' size='340' side='right'caption='[[2qiu]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2qiu]] 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=2QIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QIU 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2qiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qiu OCA], [https://pdbe.org/2qiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qiu RCSB], [https://www.ebi.ac.uk/pdbsum/2qiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qiu ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qi/2qiu_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2qiu ConSurf].
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== Publication Abstract from PubMed ==
The N-terminal glycine of the A-chain in insulin is reported to be one of the residues that binds to the insulin receptor. Modifications near this region lead to variations in the biological activity of insulin. One such modification viz., an addition of an arginine at the N-terminal A-chain, was reported to possess two-thirds the activity of native insulin. The crystal structure of 2 zinc human arg (A0) insulin has been elucidated to 2A resolution to understand the mechanism of reduction in insulin activity. A conformational transition from T6 to T3R3(f) and a decrease in the surface accessibility of residues in the so called receptor binding region have been observed. The presence of arginine has also induced distortions in the A chain N-terminal helix. The subtle conformational alterations like decrease in surface accessibility, alterations in the charge surface and changes in the relative orientation of the two helices in the A chain may be responsible for the reduction in activity.

Structural interpretation of reduced insulin activity as seen in the crystal structure of human Arg-insulin.,Sreekanth R, Pattabhi V, Rajan SS Biochimie. 2008 Mar;90(3):467-73. Epub 2007 Sep 22. PMID:18029081<ref>PMID:18029081</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2qiu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Insulin 3D Structures|Insulin 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Pattabhi V]]
[[Category: Rajan SS]]
[[Category: Sreekanth R]]