2g47

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[[Image:2g47.jpg|left|200px]]
[[Image:2g47.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2g47 |SIZE=350|CAPTION= <scene name='initialview01'>2g47</scene>, resolution 2.10&Aring;
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The line below this paragraph, containing "STRUCTURE_2g47", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= IDE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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|DOMAIN=
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{{STRUCTURE_2g47| PDB=2g47 | SCENE= }}
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|RELATEDENTRY=[[2g48|2G48]], [[2g49|2G49]], [[2g54|2G54]], [[2g56|2G56]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2g47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g47 OCA], [http://www.ebi.ac.uk/pdbsum/2g47 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2g47 RCSB]</span>
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}}
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'''Crystal structure of human insulin-degrading enzyme in complex with amyloid-beta (1-40)'''
'''Crystal structure of human insulin-degrading enzyme in complex with amyloid-beta (1-40)'''
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[[Category: Shen, Y.]]
[[Category: Shen, Y.]]
[[Category: Tang, W J.]]
[[Category: Tang, W J.]]
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[[Category: protein-peptide complex]]
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[[Category: Protein-peptide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:40:22 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:11:36 2008''
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Revision as of 01:40, 4 May 2008

Image:2g47.jpg

Template:STRUCTURE 2g47

Crystal structure of human insulin-degrading enzyme in complex with amyloid-beta (1-40)


Overview

Insulin-degrading enzyme (IDE), a Zn2+-metalloprotease, is involved in the clearance of insulin and amyloid-beta (refs 1-3). Loss-of-function mutations of IDE in rodents cause glucose intolerance and cerebral accumulation of amyloid-beta, whereas enhanced IDE activity effectively reduces brain amyloid-beta (refs 4-7). Here we report structures of human IDE in complex with four substrates (insulin B chain, amyloid-beta peptide (1-40), amylin and glucagon). The amino- and carboxy-terminal domains of IDE (IDE-N and IDE-C, respectively) form an enclosed cage just large enough to encapsulate insulin. Extensive contacts between IDE-N and IDE-C keep the degradation chamber of IDE inaccessible to substrates. Repositioning of the IDE domains enables substrate access to the catalytic cavity. IDE uses size and charge distribution of the substrate-binding cavity selectively to entrap structurally diverse polypeptides. The enclosed substrate undergoes conformational changes to form beta-sheets with two discrete regions of IDE for its degradation. Consistent with this model, mutations disrupting the contacts between IDE-N and IDE-C increase IDE catalytic activity 40-fold. The molecular basis for substrate recognition and allosteric regulation of IDE could aid in designing IDE-based therapies to control cerebral amyloid-beta and blood sugar concentrations.

About this Structure

2G47 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism., Shen Y, Joachimiak A, Rosner MR, Tang WJ, Nature. 2006 Oct 19;443(7113):870-4. Epub 2006 Oct 11. PMID:17051221 Page seeded by OCA on Sun May 4 04:40:22 2008

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