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| | ==Rat Insulin Degrading Enzyme (Insulysin)== | | ==Rat Insulin Degrading Enzyme (Insulysin)== |
| - | <StructureSection load='3p7l' size='340' side='right' caption='[[3p7l]], [[Resolution|resolution]] 2.08Å' scene=''> | + | <StructureSection load='3p7l' size='340' side='right'caption='[[3p7l]], [[Resolution|resolution]] 2.08Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p7l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P7L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P7L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p7l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P7L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.0776Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3p7o|3p7o]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ide ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3p7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p7l OCA], [https://pdbe.org/3p7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p7l RCSB], [https://www.ebi.ac.uk/pdbsum/3p7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p7l ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3p7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p7l OCA], [http://pdbe.org/3p7l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3p7l RCSB], [http://www.ebi.ac.uk/pdbsum/3p7l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3p7l ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IDE_RAT IDE_RAT]] 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. | + | [https://www.uniprot.org/uniprot/IDE_RAT IDE_RAT] 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. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | BACKGROUND: Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Abeta peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. PRINCIPAL FINDINGS: The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.
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| - | Identification of the allosteric regulatory site of insulysin.,Noinaj N, Bhasin SK, Song ES, Scoggin KE, Juliano MA, Juliano L, Hersh LB, Rodgers DW PLoS One. 2011;6(6):e20864. Epub 2011 Jun 24. PMID:21731629<ref>PMID:21731629</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3p7l" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| - | *[[Insulin-Degrading Enzyme|Insulin-Degrading Enzyme]] | + | *[[Insulin-degrading enzyme 3D structures|Insulin-degrading enzyme 3D structures]] |
| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Insulysin]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Noinaj, N]] | + | [[Category: Noinaj N]] |
| - | [[Category: Rodgers, D W]] | + | [[Category: Rodgers DW]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Peptidase]]
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