6ydx: Difference between revisions
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<StructureSection load='6ydx' size='340' side='right'caption='[[6ydx]], [[Resolution|resolution]] 3.20Å' scene=''> | <StructureSection load='6ydx' size='340' side='right'caption='[[6ydx]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ydx]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6ydx]] 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=6YDX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YDX FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ONN:2-[2-[[[(4~{R},8~{S},11~{S})-11-azanyl-8-[(4-hydroxyphenyl)methyl]-6,10-bis(oxidanylidene)-1,2-dithia-5,9-diazacyclotridec-4-yl]carbonylamino]methyl]phenyl]ethanoic+acid'>ONN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ONN:2-[2-[[[(4~{R},8~{S},11~{S})-11-azanyl-8-[(4-hydroxyphenyl)methyl]-6,10-bis(oxidanylidene)-1,2-dithia-5,9-diazacyclotridec-4-yl]carbonylamino]methyl]phenyl]ethanoic+acid'>ONN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6ydx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ydx OCA], [https://pdbe.org/6ydx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ydx RCSB], [https://www.ebi.ac.uk/pdbsum/6ydx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ydx ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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 == | ||
| Line 20: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 6ydx" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6ydx" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Giastas | [[Category: Giastas P]] | ||
[[Category: Mpakali | [[Category: Mpakali A]] | ||
[[Category: Saridakis | [[Category: Saridakis E]] | ||
[[Category: Stratikos | [[Category: Stratikos E]] | ||
Latest revision as of 16:24, 24 January 2024
Insulin-regulated aminopeptidase complexed with a macrocyclic peptidic inhibitorInsulin-regulated aminopeptidase complexed with a macrocyclic peptidic inhibitor
Structural highlights
FunctionLCAP_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 PubMedInsulin-regulated aminopeptidase (IRAP) is a transmembrane zinc metallopeptidase with many important biological functions and an emerging pharmacological target. Although previous structural studies have given insight on how IRAP recognizes linear peptides, how it recognizes its physiological cyclic ligands remains elusive. Here, we report the first crystal structure of IRAP with the macrocyclic peptide inhibitor HA08 that combines structural elements from angiotensin IV and the physiological substrates oxytocin and vasopressin. The compound is found in the catalytic site in a near canonical substrate-like configuration and inhibits by a competitive mechanism. Comparison with previously solved structures of IRAP along with small-angle X-ray scattering experiments suggests that IRAP is in an open conformation in solution but undergoes a closing conformational change upon inhibitor binding. Stabilization of the closed conformation in combination with catalytic water exclusion by the tightly juxtaposed GAMEN loop is proposed as a mechanism of inhibition. Structural Basis of Inhibition of Insulin-Regulated Aminopeptidase by a Macrocyclic Peptidic Inhibitor.,Mpakali A, Saridakis E, Giastas P, Maben Z, Stern LJ, Larhed M, Hallberg M, Stratikos E ACS Med Chem Lett. 2020 Jun 2;11(7):1429-1434. doi:, 10.1021/acsmedchemlett.0c00172. eCollection 2020 Jul 9. PMID:32676150[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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