From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:2g48.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:2g48.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_2g48| PDB=2g48 | SCENE= }} | | {{STRUCTURE_2g48| PDB=2g48 | SCENE= }} |
| | | | |
| - | '''crystal structure of human insulin-degrading enzyme in complex with amylin'''
| + | ===crystal structure of human insulin-degrading enzyme in complex with amylin=== |
| | | | |
| | | | |
| - | ==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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17051221}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17051221 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_17051221}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 26: |
Line 30: |
| | [[Category: Tang, W J.]] | | [[Category: Tang, W J.]] |
| | [[Category: Protein-peptide complex]] | | [[Category: Protein-peptide complex]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:40:26 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 02:20:51 2008'' |
Revision as of 23:20, 27 July 2008
Template:STRUCTURE 2g48
crystal structure of human insulin-degrading enzyme in complex with amylin
Template:ABSTRACT PUBMED 17051221
About this Structure
2G48 is a Protein complex structure of sequences 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 Mon Jul 28 02:20:51 2008
