2mvc: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 2mvc is ON HOLD
+==Solution structure of human insulin at pH 1.9==
+<StructureSection load='2mvc' size='340' side='right'caption='[[2mvc]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2mvc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MVC FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 50 models</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=2mvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mvc OCA], [https://pdbe.org/2mvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mvc RCSB], [https://www.ebi.ac.uk/pdbsum/2mvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mvc 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The insulin gene mutation c.137G&gt;A (R46Q), which changes an arginine at the B22 position of the mature hormone to glutamine, causes the monogenic diabetes variant maturity-onset diabetes of the young (MODY). In MODY patients, this mutation is heterozygous, and both mutant and wild-type (WT) human insulin are produced simultaneously. However, the patients often depend on administration of exogenous insulin. In this study, we chemically synthesized the MODY mutant [GlnB22]-insulin and characterized its biological and structural properties. The chemical synthesis of this insulin analogue revealed that its folding ability is severely impaired. In vitro and in vivo tests showed that its binding affinity and biological activity are reduced (both approximately 20% that of human insulin). Comparison of the solution structure of [GlnB22]-insulin with the solution structure of native human insulin revealed that the most significant structural effect of the mutation is distortion of the B20-B23 beta-turn, leading to liberation of the B chain C-terminus from the protein core. The distortion of the B20-B23 beta-turn is caused by the extended conformational freedom of the GlnB22 side chain, which is no longer anchored in a hydrogen bonding network like the native ArgB22. The partially disordered [GlnB22]-insulin structure appears to be one reason for the reduced binding potency of this mutant and may also be responsible for its low folding efficiency in vivo. The altered orientation and flexibility of the B20-B23 beta-turn may interfere with the formation of disulfide bonds in proinsulin bearing the R46Q (GlnB22) mutation. This may also have a negative effect on the WT proinsulin simultaneously biosynthesized in beta-cells and therefore play a major role in the development of MODY in patients producing [GlnB22]-insulin.
-Authors: Hexnerova, R., Krizkova, K., Maletinska, L., Jiracek, J., Brzozowski, A.M., Zakova, L., Veverka, V.
+Structural and Functional Study of the GlnB22-Insulin Mutant Responsible for Maturity-Onset Diabetes of the Young.,Krizkova K, Veverka V, Maletinska L, Hexnerova R, Brzozowski AM, Jiracek J, Zakova L PLoS One. 2014 Nov 25;9(11):e112883. doi: 10.1371/journal.pone.0112883., eCollection 2014. PMID:25423173<ref>PMID:25423173</ref>
-Description: Solution structure of human insulin at pH 1.9
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2mvc" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Insulin 3D Structures|Insulin 3D Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Brzozowski AM]]
+[[Category: Hexnerova R]]
+[[Category: Jiracek J]]
+[[Category: Krizkova K]]
+[[Category: Maletinska L]]
+[[Category: Veverka V]]
+[[Category: Zakova L]]