View source for 5ena


==Xray crystal structure of isotope-labeled human insulin==
<StructureSection load='5ena' size='340' side='right'caption='[[5ena]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ena]] is a 2 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=5ENA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ENA 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]] 1.35&#8491;</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=5ena FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ena OCA], [https://pdbe.org/5ena PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ena RCSB], [https://www.ebi.ac.uk/pdbsum/5ena PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ena 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.
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== Publication Abstract from PubMed ==
As a part of a program aimed towards the study of the dynamics of human insulin protein dimer formation using two dimensional infra red (2D-IR) spectroscopy, we have used total chemical synthesis to prepare stable isotope labeled [(1-13C=18O)PheB24)]human insulin, via [(1-13C=18O)PheB24)]ester insulin as a key intermediate product that facilitates folding of the synthetic protein molecule (see accompanying article). In the present paper, we describe the crystal structure of the synthetic isotope-labeled ester insulin intermediate and the product synthetic human insulin, and our observations on hexamer formation with these two protein molecules in the absence of phenol derivatives and/or Zn metal ions. We also describe and discuss the fractional crystallization of quasi-racemic protein mixtures containing each of these two synthetic proteins.

Crystallization of enantiomerically pure proteins from quasi-racemic mixtures: structure determination by X-ray diffraction of isotope-labeled ester insulin and human insulin.,Kent S, Mandal K, Dhayalan B, Avital-Shmilovici M, Tokmakoff A Chembiochem. 2015 Dec 28. doi: 10.1002/cbic.201500600. PMID:26707939<ref>PMID:26707939</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 5ena" style="background-color:#fffaf0;"></div>

==See Also==
*[[Insulin 3D Structures|Insulin 3D Structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Avital-Shmilovici M]]
[[Category: Dhayalan B]]
[[Category: Kent SBH]]
[[Category: Mandal K]]
[[Category: Tokmakoff A]]