5mj6

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'''Unreleased structure'''
 
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The entry 5mj6 is ON HOLD until Paper Publication
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==Ligand-induced conformational change of Insulin-regulated aminopeptidase: insights on catalytic mechanism and active site plasticity.==
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<StructureSection load='5mj6' size='340' side='right' caption='[[5mj6]], [[Resolution|resolution]] 2.53&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5mj6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MJ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MJ6 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7O2:[(2~{S})-2-[[(2~{S})-1-AZANYL-1-OXIDANYLIDENE-3-PHENYL-PROPAN-2-YL]CARBAMOYL]-4,4-DIPHENYL-BUTYL]-[(1~{R})-1-AZANYL-3-PHENYL-PROPYL]PHOSPHINIC+ACID'>7O2</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<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>
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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=5mj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mj6 OCA], [http://pdbe.org/5mj6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mj6 RCSB], [http://www.ebi.ac.uk/pdbsum/5mj6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mj6 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Insulin-regulated aminopeptidase (IRAP) is an enzyme with several important biological functions that is known to process a large variety of different peptidic substrates, although the mechanism behind this wide specificity is not clearly understood. We describe a crystal structure of IRAP in complex with a recently developed bioactive and selective inhibitor at 2.53 A resolution. In the presence of this inhibitor, the enzyme adopts a novel conformation in which domains II and IV are juxtaposed, forming a hollow structure that excludes external solvent access to the catalytic center. A loop adjacent to the enzyme's GAMEN motif undergoes structural reconfiguration, allowing the accommodation of bulky inhibitor side chains. Atomic interactions between the inhibitor and IRAP that are unique to this conformation can explain the strong selectivity compared to homologous aminopeptidases ERAP1 and ERAP2. This conformation provides insight on IRAP's catalytic cycle and reveals significant active-site plasticity that may underlie its substrate permissiveness.
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Authors: Mpakali, A., Stratikos, E., Saridakis, E., Giastas, P.
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Ligand-Induced Conformational Change of Insulin-Regulated Aminopeptidase: Insights on Catalytic Mechanism and Active Site Plasticity.,Mpakali A, Saridakis E, Harlos K, Zhao Y, Kokkala P, Georgiadis D, Giastas P, Papakyriakou A, Stratikos E J Med Chem. 2017 Apr 3. doi: 10.1021/acs.jmedchem.6b01890. PMID:28328206<ref>PMID:28328206</ref>
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Description: Ligand-induced conformational change of Insulin-regulated aminopeptidase: insights on catalytic mechanism and active site plasticity.
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Saridakis, E]]
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<div class="pdbe-citations 5mj6" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Cystinyl aminopeptidase]]
[[Category: Giastas, P]]
[[Category: Giastas, P]]
[[Category: Mpakali, A]]
[[Category: Mpakali, A]]
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[[Category: Saridakis, E]]
[[Category: Stratikos, E]]
[[Category: Stratikos, E]]
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[[Category: Endoplasmatic reticulum aminopeptidase]]
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[[Category: Generation of antigenic peptides for cross-presentation]]
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[[Category: Hydrolase]]
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[[Category: Insulin-regulated aminopeptidase]]
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[[Category: Ligand-induced conformational change]]
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[[Category: Phosphinic pseudotripeptide]]

Revision as of 13:20, 5 April 2017

Ligand-induced conformational change of Insulin-regulated aminopeptidase: insights on catalytic mechanism and active site plasticity.

5mj6, resolution 2.53Å

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