View source for 4unh


==Human insulin B26Gly mutant crystal structure==
<StructureSection load='4unh' size='340' side='right'caption='[[4unh]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4unh]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UNH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UNH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4une|4une]], [[4ung|4ung]]</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=4unh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unh OCA], [http://pdbe.org/4unh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4unh RCSB], [http://www.ebi.ac.uk/pdbsum/4unh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4unh ProSAT]</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 ==
The structural characterization of the insulin-insulin receptor (IR) interaction still lacks the conformation of the crucial B21-B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms.

Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex.,Zakova L, Kletvikova E, Lepsik M, Collinsova M, Watson CJ, Turkenburg JP, Jiracek J, Brzozowski AM Acta Crystallogr D Biol Crystallogr. 2014 Oct 1;70(Pt 10):2765-74. doi:, 10.1107/S1399004714017775. Epub 2014 Sep 27. PMID:25286859<ref>PMID:25286859</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4unh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Molecular Playground/Insulin|Molecular Playground/Insulin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Brzozowski, A M]]
[[Category: Collinsova, M]]
[[Category: Jiracek, J]]
[[Category: Klevtikova, E]]
[[Category: Lepsik, M]]
[[Category: Turkenburg, J P]]
[[Category: Watson, C J]]
[[Category: Zakova, L]]
[[Category: B26 site]]
[[Category: Hormone]]