2g56: Difference between revisions

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-[[Image:2g56.jpg|left|200px]]
- {{Structure
+==crystal structure of human insulin-degrading enzyme in complex with insulin B chain==
-|PDB= 2g56 |SIZE=350|CAPTION= <scene name='initialview01'>2g56</scene>, resolution 2.20&Aring;
+<StructureSection load='2g56' size='340' side='right'caption='[[2g56]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=DIO:1,4-DIETHYLENE DIOXIDE'>DIO</scene>
+<table><tr><td colspan='2'>[[2g56]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G56 FirstGlance]. <br>
-|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]
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
-|GENE= IDE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene></td></tr>
-}}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2g56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g56 OCA], [https://pdbe.org/2g56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g56 RCSB], [https://www.ebi.ac.uk/pdbsum/2g56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g56 ProSAT]</span></td></tr>
+</table>
-'''crystal structure of human insulin-degrading enzyme in complex with insulin B chain'''
+== Function ==
+[https://www.uniprot.org/uniprot/IDE_HUMAN IDE_HUMAN] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.<ref>PMID:10684867</ref> <ref>PMID:17613531</ref> <ref>PMID:18986166</ref>
+== Evolutionary Conservation ==
-==Overview==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g5/2g56_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2g56 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
 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==
+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<ref>PMID:17051221</ref>
-Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], Hyperproinsulinemia, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], MODY, one form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-G56 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=2G56 OCA].
+</div>
+<div class="pdbe-citations 2g56" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-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]
+*[[Insulin 3D Structures|Insulin 3D Structures]]
+*[[Insulin-degrading enzyme 3D structures|Insulin-degrading enzyme 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Insulysin]]
+[[Category: Large Structures]]
-[[Category: Protein complex]]
+[[Category: Shen Y]]
-[[Category: Shen, Y.]]
+[[Category: Tang W-J]]
-[[Category: Tang, W J.]]
-[[Category: DIO]]
-[[Category: protein-peptide complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:00:38 2008''