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2g54

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[[Image:2g54.jpg|left|200px]]<br /><applet load="2g54" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2g54.jpg|left|200px]]
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caption="2g54, resolution 2.25&Aring;" />
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'''Crystal structure of Zn-bound human insulin-degrading enzyme in complex with insulin B chain'''<br />
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{{Structure
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|PDB= 2g54 |SIZE=350|CAPTION= <scene name='initialview01'>2g54</scene>, resolution 2.25&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=DIO:1,4-DIETHYLENE DIOXIDE'>DIO</scene>
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|ACTIVITY= [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]
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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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}}
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'''Crystal structure of Zn-bound human insulin-degrading enzyme in complex with insulin B chain'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2G54 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=ZN:'>ZN</scene> and <scene name='pdbligand=DIO:'>DIO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=2G54 OCA].
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2G54 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G54 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17051221 17051221]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/17051221 17051221]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Insulysin]]
[[Category: Insulysin]]
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[[Category: protein-peptide complex]]
[[Category: protein-peptide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:28:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:00:32 2008''

Revision as of 15:00, 20 March 2008

Image:2g54.jpg


PDB ID 2g54

Drag the structure with the mouse to rotate
, resolution 2.25Å
Ligands: and
Gene: IDE (Homo sapiens)
Activity: Insulysin, with EC number 3.4.24.56
Coordinates: save as pdb, mmCIF, xml



Crystal structure of Zn-bound human insulin-degrading enzyme in complex with insulin B chain


Contents

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.

Disease

Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]

About this Structure

2G54 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

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