2g48: Difference between revisions
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'''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 DIO 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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