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| | <StructureSection load='4p8q' size='340' side='right'caption='[[4p8q]], [[Resolution|resolution]] 3.02Å' scene=''> | | <StructureSection load='4p8q' size='340' side='right'caption='[[4p8q]], [[Resolution|resolution]] 3.02Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4p8q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P8Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P8Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4p8q]] is a 2 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=4P8Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P8Q FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LNPEP, OTASE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4p8q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p8q OCA], [https://pdbe.org/4p8q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p8q RCSB], [https://www.ebi.ac.uk/pdbsum/4p8q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p8q 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/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=4p8q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p8q OCA], [http://pdbe.org/4p8q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p8q RCSB], [http://www.ebi.ac.uk/pdbsum/4p8q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p8q ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LCAP_HUMAN LCAP_HUMAN]] Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain.<ref>PMID:11389728</ref> <ref>PMID:11707427</ref> <ref>PMID:1731608</ref> | + | [https://www.uniprot.org/uniprot/LCAP_HUMAN LCAP_HUMAN] Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain.<ref>PMID:11389728</ref> <ref>PMID:11707427</ref> <ref>PMID:1731608</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cystinyl aminopeptidase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ascher, D B]] | + | [[Category: Ascher DB]] |
| - | [[Category: Hancock, N C]] | + | [[Category: Hancock NC]] |
| - | [[Category: Hermans, S J]] | + | [[Category: Hermans SJ]] |
| - | [[Category: Holien, J K]] | + | [[Category: Holien JK]] |
| - | [[Category: Michell, B]] | + | [[Category: Michell B]] |
| - | [[Category: Morton, C J]] | + | [[Category: Morton CJ]] |
| - | [[Category: Parker, M W]] | + | [[Category: Parker MW]] |
| - | [[Category: Aminopeptidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metallopeptidase]]
| + | |
| Structural highlights
Function
LCAP_HUMAN Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain.[1] [2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Matsumoto H, Nagasaka T, Hattori A, Rogi T, Tsuruoka N, Mizutani S, Tsujimoto M. Expression of placental leucine aminopeptidase/oxytocinase in neuronal cells and its action on neuronal peptides. Eur J Biochem. 2001 Jun;268(11):3259-66. PMID:11389728
- ↑ Albiston AL, McDowall SG, Matsacos D, Sim P, Clune E, Mustafa T, Lee J, Mendelsohn FA, Simpson RJ, Connolly LM, Chai SY. Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. J Biol Chem. 2001 Dec 28;276(52):48623-6. Epub 2001 Nov 13. PMID:11707427 doi:http://dx.doi.org/10.1074/jbc.C100512200
- ↑ Tsujimoto M, Mizutani S, Adachi H, Kimura M, Nakazato H, Tomoda Y. Identification of human placental leucine aminopeptidase as oxytocinase. Arch Biochem Biophys. 1992 Feb 1;292(2):388-92. PMID:1731608
- ↑ Hermans SJ, Ascher DB, Hancock NC, Holien JK, Michell BJ, Chai SY, Morton CJ, Parker MW. Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides. Protein Sci. 2014 Nov 18. doi: 10.1002/pro.2604. PMID:25408552 doi:http://dx.doi.org/10.1002/pro.2604
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