5k1v

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Endoplasmic Reticulum aminopeptidase 2 (ERAP2) in complex with a diaminobenzoic acid derivative ligand.

Structural highlights

5k1v is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.897Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Endoplasmic 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.

References

↑ Tanioka T, Hattori A, Masuda S, Nomura Y, Nakayama H, Mizutani S, Tsujimoto M. Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases. J Biol Chem. 2003 Aug 22;278(34):32275-83. Epub 2003 Jun 10. PMID:12799365 doi:http://dx.doi.org/10.1074/jbc.M305076200
↑ Saveanu L, Carroll O, Lindo V, Del Val M, Lopez D, Lepelletier Y, Greer F, Schomburg L, Fruci D, Niedermann G, van Endert PM. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat Immunol. 2005 Jul;6(7):689-97. Epub 2005 May 22. PMID:15908954 doi:http://dx.doi.org/10.1038/ni1208
↑ Chang SC, Momburg F, Bhutani N, Goldberg AL. The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a "molecular ruler" mechanism. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17107-12. Epub 2005 Nov 14. PMID:16286653 doi:http://dx.doi.org/0500721102
↑ Mpakali A, Giastas P, Deprez-Poulain R, Papakyriakou A, Koumantou D, Gealageas R, Tsoukalidou S, Vourloumis D, Mavridis IM, Stratikos E, Saridakis E. Crystal Structures of ERAP2 Complexed with Inhibitors Reveal Pharmacophore Requirements for Optimizing Inhibitor Potency. ACS Med Chem Lett. 2017 Feb 21;8(3):333-337. doi: 10.1021/acsmedchemlett.6b00505., eCollection 2017 Mar 9. PMID:28337326 doi:http://dx.doi.org/10.1021/acsmedchemlett.6b00505

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5k1v"

@@ Line 1: / Line 1: @@
 ==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]] 2.90&Aring;' scene=''>
+<StructureSection load='5k1v' size='340' side='right'caption='[[5k1v]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K1V FirstGlance]. <br>
+<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]] 2.897&#8491;</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=5k1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k1v OCA], [http://pdbe.org/5k1v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k1v RCSB], [http://www.ebi.ac.uk/pdbsum/5k1v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k1v ProSAT]</span></td></tr>
+<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>
 == Function ==
-[[http://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>
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5k1v" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Giastas, P]]
+[[Category: Homo sapiens]]
-[[Category: Mavridis, I M]]
+[[Category: Large Structures]]
-[[Category: Mpakali, A]]
+[[Category: Giastas P]]
-[[Category: Papakyriakou, A]]
+[[Category: Mavridis IM]]
-[[Category: Saridakis, E]]
+[[Category: Mpakali A]]
-[[Category: Stratikos, E]]
+[[Category: Papakyriakou A]]
-[[Category: Diaminobenzoic acid derivative]]
+[[Category: Saridakis E]]
-[[Category: Endoplasmic reticulum aminopeptidase]]
+[[Category: Stratikos E]]
-[[Category: Hydrolase]]
-[[Category: Zinc-binding metallopeptidase]]

5k1v

From Proteopedia

Current revision

Crystal structure of Endoplasmic Reticulum aminopeptidase 2 (ERAP2) in complex with a diaminobenzoic acid derivative ligand.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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