4pj6: Difference between revisions
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''' | ==Crystal Structure of Human Insulin Regulated Aminopeptidase with Lysine in Active Site== | ||
<StructureSection load='4pj6' size='340' side='right' caption='[[4pj6]], [[Resolution|resolution]] 2.96Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4pj6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PJ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PJ6 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cystinyl_aminopeptidase Cystinyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.3 3.4.11.3] </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=4pj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pj6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pj6 RCSB], [http://www.ebi.ac.uk/pdbsum/4pj6 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Insulin-regulated aminopeptidase (IRAP, or oxytocinase) is a membrane-bound zinc- metallopeptidase that cleaves neuroactive peptides in the brain and produces memory enhancing effects when inhibited. We have determined the crystal structure of human IRAP revealing a closed, four domain arrangement with a large, mostly buried cavity abutting the active site. The structure reveals that the GAMEN exopeptidase loop adopts a very different conformation from other aminopeptidases, thus explaining IRAP's unique specificity for cyclic peptides such as oxytocin and vasopressin. Computational docking of a series of IRAP-specific cognitive enhancers into the crystal structure provides a molecular basis for their structure-activity relationships and demonstrates that the structure will be a powerful tool in the development of new classes of cognitive enhancers for treating a variety of memory disorders such as Alzheimer's disease. This article is protected by copyright. All rights reserved. | |||
Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides.,Hermans SJ, Ascher DB, Hancock NC, Holien JK, Michell BJ, Chai SY, Morton CJ, Parker MW Protein Sci. 2014 Nov 18. doi: 10.1002/pro.2604. PMID:25408552<ref>PMID:25408552</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cystinyl aminopeptidase]] | |||
[[Category: Ascher, D B]] | |||
[[Category: Hancock, N C]] | |||
[[Category: Hermans, S J]] | |||
[[Category: Holien, J K]] | |||
[[Category: Michell, B]] | |||
[[Category: Morton, C J]] | |||
[[Category: Parker, M W]] | |||
[[Category: Aminopeptidase]] | |||
[[Category: Hydrolase]] | |||
[[Category: Metalloprotease]] | |||
Revision as of 12:28, 3 December 2014
Crystal Structure of Human Insulin Regulated Aminopeptidase with Lysine in Active SiteCrystal Structure of Human Insulin Regulated Aminopeptidase with Lysine in Active Site
Structural highlights
Publication Abstract from PubMedInsulin-regulated aminopeptidase (IRAP, or oxytocinase) is a membrane-bound zinc- metallopeptidase that cleaves neuroactive peptides in the brain and produces memory enhancing effects when inhibited. We have determined the crystal structure of human IRAP revealing a closed, four domain arrangement with a large, mostly buried cavity abutting the active site. The structure reveals that the GAMEN exopeptidase loop adopts a very different conformation from other aminopeptidases, thus explaining IRAP's unique specificity for cyclic peptides such as oxytocin and vasopressin. Computational docking of a series of IRAP-specific cognitive enhancers into the crystal structure provides a molecular basis for their structure-activity relationships and demonstrates that the structure will be a powerful tool in the development of new classes of cognitive enhancers for treating a variety of memory disorders such as Alzheimer's disease. This article is protected by copyright. All rights reserved. Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides.,Hermans SJ, Ascher DB, Hancock NC, Holien JK, Michell BJ, Chai SY, Morton CJ, Parker MW Protein Sci. 2014 Nov 18. doi: 10.1002/pro.2604. PMID:25408552[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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