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2g47

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{{STRUCTURE_2g47| PDB=2g47 | SCENE= }}
{{STRUCTURE_2g47| PDB=2g47 | SCENE= }}
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'''Crystal structure of human insulin-degrading enzyme in complex with amyloid-beta (1-40)'''
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===Crystal structure of human insulin-degrading enzyme in complex with amyloid-beta (1-40)===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17051221 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17051221}}
==About this Structure==
==About this Structure==
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[[Category: Tang, W J.]]
[[Category: Tang, W J.]]
[[Category: Protein-peptide complex]]
[[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 Sun Jul 27 16:58:25 2008''

Revision as of 13:58, 27 July 2008

Image:2g47.png

Template:STRUCTURE 2g47

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

Template:ABSTRACT PUBMED 17051221

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

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