5azz: Difference between revisions
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==Crystal structure of seleno-insulin== | |||
<StructureSection load='5azz' size='340' side='right'caption='[[5azz]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5azz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AZZ FirstGlance]. <br> | |||
</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=5azz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5azz OCA], [https://pdbe.org/5azz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5azz RCSB], [https://www.ebi.ac.uk/pdbsum/5azz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5azz ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/INS_BOVIN INS_BOVIN] 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 == | |||
Synthetic insulin analogues with a long lifetime are current drug targets for the therapy of diabetic patients. The replacement of the interchain disulfide with a diselenide bridge, which is more resistant to reduction and internal bond rotation, can enhance the lifetime of insulin in the presence of the insulin-degrading enzyme (IDE) without impairing the hormonal function. The [C7UA ,C7UB ] variant of bovine pancreatic insulin (BPIns) was successfully prepared by using two selenocysteine peptides (i.e., the C7U analogues of A- and B-chains, respectively). In a buffer solution at pH 10 they spontaneously assembled under thermodynamic control to the correct insulin fold. The selenoinsulin (Se-Ins) exhibited a bioactivity comparable to that of BPIns. Interestingly, degradation of Se-Ins with IDE was significantly decelerated (tau1/2 approximately 8 h vs. approximately 1 h for BPIns). The lifetime enhancement could be due to both the intrinsic stability of the diselenide bond and local conformational changes induced by the substitution. | |||
Preparation of Selenoinsulin as a Long-Lasting Insulin Analogue.,Arai K, Takei T, Okumura M, Watanabe S, Amagai Y, Asahina Y, Moroder L, Hojo H, Inaba K, Iwaoka M Angew Chem Int Ed Engl. 2017 May 8;56(20):5522-5526. doi: 10.1002/anie.201701654., Epub 2017 Apr 10. PMID:28394477<ref>PMID:28394477</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5azz" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Insulin 3D Structures|Insulin 3D Structures]] | ||
[[Category: | == References == | ||
[[Category: Okumura | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Watanabe | </StructureSection> | ||
[[Category: Bos taurus]] | |||
[[Category: Large Structures]] | |||
[[Category: Arai K]] | |||
[[Category: Asahina Y]] | |||
[[Category: Hojo H]] | |||
[[Category: Inaba K]] | |||
[[Category: Iwaoka M]] | |||
[[Category: Okumura M]] | |||
[[Category: Takei T]] | |||
[[Category: Watanabe S]] | |||
Latest revision as of 09:33, 31 May 2023
Crystal structure of seleno-insulinCrystal structure of seleno-insulin
Structural highlights
FunctionINS_BOVIN 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. Publication Abstract from PubMedSynthetic insulin analogues with a long lifetime are current drug targets for the therapy of diabetic patients. The replacement of the interchain disulfide with a diselenide bridge, which is more resistant to reduction and internal bond rotation, can enhance the lifetime of insulin in the presence of the insulin-degrading enzyme (IDE) without impairing the hormonal function. The [C7UA ,C7UB ] variant of bovine pancreatic insulin (BPIns) was successfully prepared by using two selenocysteine peptides (i.e., the C7U analogues of A- and B-chains, respectively). In a buffer solution at pH 10 they spontaneously assembled under thermodynamic control to the correct insulin fold. The selenoinsulin (Se-Ins) exhibited a bioactivity comparable to that of BPIns. Interestingly, degradation of Se-Ins with IDE was significantly decelerated (tau1/2 approximately 8 h vs. approximately 1 h for BPIns). The lifetime enhancement could be due to both the intrinsic stability of the diselenide bond and local conformational changes induced by the substitution. Preparation of Selenoinsulin as a Long-Lasting Insulin Analogue.,Arai K, Takei T, Okumura M, Watanabe S, Amagai Y, Asahina Y, Moroder L, Hojo H, Inaba K, Iwaoka M Angew Chem Int Ed Engl. 2017 May 8;56(20):5522-5526. doi: 10.1002/anie.201701654., Epub 2017 Apr 10. PMID:28394477[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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