2g48
From Proteopedia
(New page: 200px<br /> <applet load="2g48" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g48, resolution 2.60Å" /> '''crystal structure o...) |
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| - | [[Image:2g48. | + | [[Image:2g48.jpg|left|200px]]<br /><applet load="2g48" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2g48, resolution 2.60Å" /> | caption="2g48, resolution 2.60Å" /> | ||
'''crystal structure of human insulin-degrading enzyme in complex with amylin'''<br /> | '''crystal structure of human insulin-degrading enzyme in complex with amylin'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2G48 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with DIO as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 2G48 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=DIO:'>DIO</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G48 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein-peptide complex]] | [[Category: protein-peptide complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:27:05 2008'' |
Revision as of 15:27, 15 February 2008
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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.
About this Structure
2G48 is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Insulysin, with EC number 3.4.24.56 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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