5k1v: Difference between revisions
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==Crystal structure of Endoplasmic Reticulum aminopeptidase 2 (ERAP2) in complex with a diaminobenzoic acid derivative ligand.== | ==Crystal structure of Endoplasmic Reticulum aminopeptidase 2 (ERAP2) in complex with a diaminobenzoic acid derivative ligand.== | ||
<StructureSection load='5k1v' size='340' side='right' caption='[[5k1v]], [[Resolution|resolution]] 2.90Å' scene=''> | <StructureSection load='5k1v' size='340' side='right'caption='[[5k1v]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5k1v]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K1V OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5k1v]] 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=5K1V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K1V FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6PX:METHYL+N-[4-AMINO-3-(L-ARGINYLAMINO)BENZENE-1-CARBONYL]-L-TYROSINATE'>6PX</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> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.897Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6PX:METHYL+N-[4-AMINO-3-(L-ARGINYLAMINO)BENZENE-1-CARBONYL]-L-TYROSINATE'>6PX</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> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5k1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k1v OCA], [https://pdbe.org/5k1v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k1v RCSB], [https://www.ebi.ac.uk/pdbsum/5k1v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k1v ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ERAP2_HUMAN ERAP2_HUMAN] Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Preferentially hydrolyzes the basic residues Arg and Lys.<ref>PMID:12799365</ref> <ref>PMID:15908954</ref> <ref>PMID:16286653</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5k1v" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5k1v" 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: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Giastas P]] | ||
[[Category: | [[Category: Mavridis IM]] | ||
[[Category: | [[Category: Mpakali A]] | ||
[[Category: | [[Category: Papakyriakou A]] | ||
[[Category: | [[Category: Saridakis E]] | ||
[[Category: | [[Category: Stratikos E]] | ||
Latest revision as of 22:18, 20 September 2023
Crystal structure of Endoplasmic Reticulum aminopeptidase 2 (ERAP2) in complex with a diaminobenzoic acid derivative ligand.Crystal structure of Endoplasmic Reticulum aminopeptidase 2 (ERAP2) in complex with a diaminobenzoic acid derivative ligand.
Structural highlights
FunctionERAP2_HUMAN Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Preferentially hydrolyzes the basic residues Arg and Lys.[1] [2] [3] Publication Abstract from PubMedEndoplasmic reticulum aminopeptidase 2 assists with the generation of antigenic peptides for presentation onto Major Histocompatibility Class I molecules in humans. Recent evidence has suggested that the activity of ERAP2 may contribute to the generation of autoimmunity, thus making ERAP2 a possible pharmacological target for the regulation of adaptive immune responses. To better understand the structural elements of inhibitors that govern their binding affinity to the ERAP2 active site, we cocrystallized ERAP2 with a medium activity 3,4-diaminobenzoic acid inhibitor and a poorly active hydroxamic acid derivative. Comparison of these two crystal structures with a previously solved structure of ERAP2 in complex with a potent phosphinic pseudopeptide inhibitor suggests that engaging the substrate N-terminus recognition properties of the active site is crucial for inhibitor binding even in the absence of a potent zinc-binding group. Proper utilization of all five major pharmacophores is necessary, however, to optimize inhibitor potency. Crystal Structures of ERAP2 Complexed with Inhibitors Reveal Pharmacophore Requirements for Optimizing Inhibitor Potency.,Mpakali A, Giastas P, Deprez-Poulain R, Papakyriakou A, Koumantou D, Gealageas R, Tsoukalidou S, Vourloumis D, Mavridis IM, Stratikos E, Saridakis E ACS Med Chem Lett. 2017 Feb 21;8(3):333-337. doi: 10.1021/acsmedchemlett.6b00505., eCollection 2017 Mar 9. PMID:28337326[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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