3p7o: Difference between revisions
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[[ | ==Rat Insulin Degrading Enzyme (Insulysin) E111F mutant with two bound peptides== | ||
<StructureSection load='3p7o' size='340' side='right' caption='[[3p7o]], [[Resolution|resolution]] 2.14Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3p7o]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P7O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P7O FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</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 Rattus norvegicus])</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> | |||
<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=3p7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p7o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p7o RCSB], [http://www.ebi.ac.uk/pdbsum/3p7o PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Insulin-Degrading Enzyme|Insulin-Degrading Enzyme]] | *[[Insulin-Degrading Enzyme|Insulin-Degrading Enzyme]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Insulysin]] | [[Category: Insulysin]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Noinaj, N | [[Category: Noinaj, N]] | ||
[[Category: Rodgers, D W | [[Category: Rodgers, D W]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Metallopeptidase]] | [[Category: Metallopeptidase]] | ||
Revision as of 10:57, 9 December 2014
Rat Insulin Degrading Enzyme (Insulysin) E111F mutant with two bound peptides
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