Insulin-Degrading Enzyme: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 38: | Line 38: | ||
The enclosed substrate undergoes conformational changes to form β-sheets with two discrete regions of IDE for its degradation. | The enclosed substrate undergoes conformational changes to form β-sheets with two discrete regions of IDE for its degradation. | ||
IDE-N and IDE-C have extensive interactions that bury a large surface of 11,496 Ȧ<sup>2</sup> with good shape complementarity and numerous hydrogen bonds. In the absence of interactions with factors or proteins, the substrate-free IDE-c state is stable and the catalytic chamber of IDE is mostly closed. So we can consider that IDE-c is the resting and inactive state of IDE. | IDE-N and IDE-C have extensive interactions that bury a large surface of 11,496 Ȧ<sup>2</sup> with good shape complementarity and numerous hydrogen bonds. In the absence of interactions with factors or proteins, the substrate-free IDE-c state is stable and the catalytic chamber of IDE is mostly closed. So we can consider that IDE-c is the resting and inactive state of IDE. | ||
=== Han ethnicity-specific type 2 diabetic treatment from traditional Chinese medicine? <ref>doi 10.1080/07391102.2012.732340</ref>=== | |||
Insulin-degrading enzyme (IDE) is a zinc-metalloendopeptidase found mostly in cytosol. Since overexpression of IDE increases the rate of extracellular insulin degradation, IDE is a potential target for controlling insulin degradation. | |||
The <scene name='Journal:JBSD:29/Cv/3'>binding site of IDE protein bound with insulin</scene> (<span style="color:cyan;background-color:black;font-weight:bold;">IDE protein colored in cyan</span> and <font color='darkmagenta'><b>insulin colored in darkmagenta</b></font>) is shown by the crystal structure [[2g54]]. Leissring ''et al.'' (2010)<ref name="Leissring">PMID:20498699</ref> also indicated a <scene name='Journal:JBSD:29/Cv/4'>series of residues</scene> (<span style="color:orange;background-color:black;font-weight:bold;">colored in orange</span>) and zinc ion in the catalytic site of IDE protein which interacted with their IDE inhibitors. | |||
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. | |||
</StructureSection> | </StructureSection> | ||
__NOTOC__ | __NOTOC__ | ||
| Line 75: | Line 82: | ||
<ref group="xtra">PMID:17051221</ref><references group="xtra"/> | <ref group="xtra">PMID:17051221</ref><references group="xtra"/> | ||
<ref group="xtra">PMID: 16574064</ref><references group="xtra"/> | <ref group="xtra">PMID: 16574064</ref><references group="xtra"/> | ||
<references/> | |||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||