Insulin-Degrading Enzyme: Difference between revisions
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Virtual screening of the IDE protein (PDB ID: [[2jg4]]) was conducted using the binding site defined by the catalytic site of IDE protein. In silico results indicate that traditional Chinese medicine compounds <scene name='Journal:JBSD:29/Cv/5'>dihydrocaffeic acid</scene> (<span style="color:royalblue;background-color:black;font-weight:bold;">colored in royalblue</span>), <scene name='Journal:JBSD:29/Cv/6'>isopraeroside IV</scene> (<font color='blueviolet'><b>colored in blueviolet</b></font>), and <scene name='Journal:JBSD:29/Cv/8'>scopolin</scene> (<span style="color:chocolate;background-color:black;font-weight:bold;">colored in chocolate</span>) had high binding affinity with IDE protein and formed hydrogen bonds with the key active residue, <font color='magenta'><b>Glu111 (colored in magenta)</b></font> and <span style="color:lime;background-color:black;font-weight:bold;">other residues in the IDE binding site (colored in green)</span>. As the top three TCM compounds had stable interactions with zinc cation and residues in the catalytic site of IDE, they may block binding of other substrates, such as insulin, to the catalytic site. This competitive binding may limit the degradation of insulin. The top TCM candidates, dihydrocaffeic acid, isopraeroside IV, and scopolin, may have potential to be lead compounds for controlling insulin degradation for type 2 diabetes mellitus. | Virtual screening of the IDE protein (PDB ID: [[2jg4]]) was conducted using the binding site defined by the catalytic site of IDE protein. In silico results indicate that traditional Chinese medicine compounds <scene name='Journal:JBSD:29/Cv/5'>dihydrocaffeic acid</scene> (<span style="color:royalblue;background-color:black;font-weight:bold;">colored in royalblue</span>), <scene name='Journal:JBSD:29/Cv/6'>isopraeroside IV</scene> (<font color='blueviolet'><b>colored in blueviolet</b></font>), and <scene name='Journal:JBSD:29/Cv/8'>scopolin</scene> (<span style="color:chocolate;background-color:black;font-weight:bold;">colored in chocolate</span>) had high binding affinity with IDE protein and formed hydrogen bonds with the key active residue, <font color='magenta'><b>Glu111 (colored in magenta)</b></font> and <span style="color:lime;background-color:black;font-weight:bold;">other residues in the IDE binding site (colored in green)</span>. As the top three TCM compounds had stable interactions with zinc cation and residues in the catalytic site of IDE, they may block binding of other substrates, such as insulin, to the catalytic site. This competitive binding may limit the degradation of insulin. The top TCM candidates, dihydrocaffeic acid, isopraeroside IV, and scopolin, may have potential to be lead compounds for controlling insulin degradation for type 2 diabetes mellitus. | ||
==3D structures of insulin-degrading enzyme== | |||
[[Insulin-degrading enzyme 3D structures]] | |||
</StructureSection> | </StructureSection> | ||
__NOTOC__ | __NOTOC__ | ||
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**[[3p7l]] - rIDE – rat<br /> | **[[3p7l]] - rIDE – rat<br /> | ||
*Insulin-degrading enzyme complexes | *Insulin-degrading enzyme binary complexes | ||
**[[3n56]], [[3n57]] – hIDE (mutant) + B-type natriuretic peptide <br /> | **[[3n56]], [[3n57]] – hIDE (mutant) + B-type natriuretic peptide <br /> | ||
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**[[2jbu]] - hIDE (mutant) + co-purified peptide<br /> | **[[2jbu]] - hIDE (mutant) + co-purified peptide<br /> | ||
**[[2g47]], [[2wk3]] - hIDE (mutant) + amyloid β A4 residues 1-40<br /> | **[[2g47]], [[2wk3]] - hIDE (mutant) + amyloid β A4 residues 1-40<br /> | ||
**[[2g49]] - hIDE (mutant) + glucagons<br /> | **[[2g49]] - hIDE (mutant) + glucagons<br /> | ||
**[[2g56]] - hIDE + insulin β chain <br /> | **[[2g56]] - hIDE + insulin β chain <br /> | ||
**[[4dtt]], [[4dwk]], [[4nxo]], [[4qia]] – hIDE + inhibitor<br /> | **[[4dtt]], [[4dwk]], [[4nxo]], [[4qia]] – hIDE + inhibitor<br /> | ||
**[[4gs8]], [[4gsc]], [[4gsf]], [[4ifh]], [[2ypu]], [[4lte]], [[4pf7]], [[4pf9]], [[4pfc]], [[4re9]] - hIDE (mutant) + inhibitor<br /> | **[[4gs8]], [[4gsc]], [[4gsf]], [[4ifh]], [[2ypu]], [[4lte]], [[4pf7]], [[4pf9]], [[4pfc]], [[4re9]], [[6mq3]] - hIDE (mutant) + inhibitor<br /> | ||
**[[3p7o]] - rIDE (mutant) + peptide<br /> | **[[3p7o]] - rIDE (mutant) + peptide<br /> | ||
**[[4iof]] – hIDE + antibody<br /> | **[[4iof]] – hIDE + antibody<br /> | ||
**[[5uoe]] – hIDE (mutant) + antibody <br /> | **[[5uoe]] – hIDE (mutant) + antibody <br /> | ||
**[[6bf7]], [[6bf9]] – hIDE + antibody – Cryo EM<br /> | **[[6bf7]], [[6bf9]], [[6b7z]] – hIDE + antibody – Cryo EM<br /> | ||
**[[6bf8]], [[6bfc]], [[6b3q]] – hIDE + insulin – Cryo EM<br /> | **[[6bf8]], [[6bfc]], [[6b3q]] – hIDE + insulin – Cryo EM<br /> | ||
*Insulin-degrading enzyme ternary complexes | |||
**[[4m1c]] – hIDE + antibody + amyloid β A4 protein residues 1-40<br /> | |||
**[[6eds]] - hIDE (mutant) + glucagon + inhibitor<br /> | |||
**[[2g54]] - hIDE (mutant) + insulin chain + Zn<br /> | |||
**[[4pes]], [[6byz]] - hIDE (mutant) + inhibitor + tripeptide<br /> | |||
**[[6b70]] – hIDE + antibody + insulin – Cryo EM<br /> | **[[6b70]] – hIDE + antibody + insulin – Cryo EM<br /> | ||
**[[ | **[[4q5z]] – hIDE + antibody + insulin<br /> | ||
**[[5cjo]] – hIDE (mutant) + antibody + insulin<br /> | **[[5cjo]] – hIDE (mutant) + antibody + insulin<br /> | ||
**[[3tuv]] - rIDE + peptide + ATP | **[[3tuv]] - rIDE + peptide + ATP | ||
}} | }} | ||