4e36 - Revision history

OCA at 08:19, 9 October 2024

2024-10-09T08:19:02Z

← Older revision		Revision as of 08:19, 9 October 2024
Line 10:		Line 10:
	== 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>		[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 ==
			Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2) cooperate to trim antigenic peptide precursors for loading onto MHC class I molecules and help regulate the adaptive immune response. Common coding single nucleotide polymorphisms in ERAP1 and ERAP2 have been linked with predisposition to human diseases ranging from viral and bacterial infections to autoimmunity and cancer. It has been hypothesized that altered Ag processing by these enzymes is a causal link to disease etiology, but the molecular mechanisms are obscure. We report in this article that the common ERAP2 single nucleotide polymorphism rs2549782 that codes for amino acid variation N392K leads to alterations in both the activity and the specificity of the enzyme. Specifically, the 392N allele excises hydrophobic N-terminal residues from epitope precursors up to 165-fold faster compared with the 392K allele, although both alleles are very similar in excising positively charged N-terminal amino acids. These effects are primarily due to changes in the catalytic turnover rate (k(cat)) and not in the affinity for the substrate. X-ray crystallographic analysis of the ERAP2 392K allele suggests that the polymorphism interferes with the stabilization of the N terminus of the peptide both directly and indirectly through interactions with key residues participating in catalysis. This specificity switch allows the 392N allele of ERAP2 to supplement ERAP1 activity for the removal of hydrophobic N-terminal residues. Our results provide mechanistic insight to the association of this ERAP2 polymorphism with disease and support the idea that polymorphic variation in Ag processing enzymes constitutes a component of immune response variability in humans.

			A common single nucleotide polymorphism in endoplasmic reticulum aminopeptidase 2 induces a specificity switch that leads to altered antigen processing.,Evnouchidou I, Birtley J, Seregin S, Papakyriakou A, Zervoudi E, Samiotaki M, Panayotou G, Giastas P, Petrakis O, Georgiadis D, Amalfitano A, Saridakis E, Mavridis IM, Stratikos E J Immunol. 2012 Sep 1;189(5):2383-92. Epub 2012 Jul 25. PMID:22837489<ref>PMID:22837489</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4e36" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 14:50, 14 March 2024

2024-03-14T14:50:58Z

← Older revision		Revision as of 14:50, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e36]] 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=4E36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E36 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e36]] 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=4E36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E36 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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]] 3.22Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=4e36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e36 OCA], [https://pdbe.org/4e36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e36 RCSB], [https://www.ebi.ac.uk/pdbsum/4e36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e36 ProSAT]</span></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=4e36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e36 OCA], [https://pdbe.org/4e36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e36 RCSB], [https://www.ebi.ac.uk/pdbsum/4e36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e36 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>		[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 ==~~
	Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2) cooperate to trim antigenic peptide precursors for loading onto MHC class I molecules and help regulate the adaptive immune response. Common coding single nucleotide polymorphisms in ERAP1 and ERAP2 have been linked with predisposition to human diseases ranging from viral and bacterial infections to autoimmunity and cancer. It has been hypothesized that altered Ag processing by these enzymes is a causal link to disease etiology, but the molecular mechanisms are obscure. We report in this article that the common ERAP2 single nucleotide polymorphism rs2549782 that codes for amino acid variation N392K leads to alterations in both the activity and the specificity of the enzyme. Specifically, the 392N allele excises hydrophobic N-terminal residues from epitope precursors up to 165-fold faster compared with the 392K allele, although both alleles are very similar in excising positively charged N-terminal amino acids. These effects are primarily due to changes in the catalytic turnover rate (k(cat)) and not in the affinity for the substrate. X-ray crystallographic analysis of the ERAP2 392K allele suggests that the polymorphism interferes with the stabilization of the N terminus of the peptide both directly and indirectly through interactions with key residues participating in catalysis. This specificity switch allows the 392N allele of ERAP2 to supplement ERAP1 activity for the removal of hydrophobic N-terminal residues. Our results provide mechanistic insight to the association of this ERAP2 polymorphism with disease and support the idea that polymorphic variation in Ag processing enzymes constitutes a component of immune response variability in humans.

	A common single nucleotide polymorphism in endoplasmic reticulum aminopeptidase 2 induces a specificity switch that leads to altered antigen processing.,Evnouchidou I, Birtley J, Seregin S, Papakyriakou A, Zervoudi E, Samiotaki M, Panayotou G, Giastas P, Petrakis O, Georgiadis D, Amalfitano A, Saridakis E, Mavridis IM, Stratikos E J Immunol. 2012 Sep 1;189(5):2383-92. Epub 2012 Jul 25. PMID:22837489<ref>PMID:22837489</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4e36" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==

OCA at 06:47, 28 September 2022

2022-09-28T06:47:10Z

← Older revision		Revision as of 06:47, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2 variant N392K==		==Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2 variant N392K==
	<StructureSection load='4e36' size='340' side='right' caption='[[4e36]], [[Resolution\|resolution]] 3.22Å' scene=''>		<StructureSection load='4e36' size='340' side='right'caption='[[4e36]], [[Resolution\|resolution]] 3.22Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e36]] 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=4E36 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E36 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e36]] 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=4E36 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E36 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3se6\|3se6]]</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=4e36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e36 OCA], [https://pdbe.org/4e36 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e36 RCSB], [https://www.ebi.ac.uk/pdbsum/4e36 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e36 ProSAT]</span></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERAP2, Irap, LRAP ([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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4e36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e36 OCA], [~~http~~://pdbe.org/4e36 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e36 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e36 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e36 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4e36" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4e36" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Aminopeptidase 3D structures\|Aminopeptidase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Birtley~~, J R~~]]		[[Category: Large Structures]]
	[[Category: Mavridis~~, I M~~]]		[[Category: Birtley JR]]
	[[Category: Pegias, P]]		[[Category: Mavridis IM]]
	[[Category: Saridakis, E]]		[[Category: Pegias P]]
	[[Category: Stratikos, E]]		[[Category: Saridakis E]]
	~~[[Category: Aminopeptidase]]~~		[[Category: Stratikos E]]
	~~[[Category: Endoplasmic reticulum]]~~
	~~[[Category: Glycosylation]]~~
	~~[[Category: Hydrolase]]~~
	~~[[Category: Thermolysin-like catalytic domain]]~~
	~~[[Category: Zinc binding~~]]

OCA at 07:59, 15 November 2017

2017-11-15T07:59:02Z

← Older revision		Revision as of 07:59, 15 November 2017
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e36]] 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=4E36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E36 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e36]] 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=4E36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E36 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN~~</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN~~</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3se6\|3se6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3se6\|3se6]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERAP2, Irap, LRAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERAP2, Irap, LRAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4e36" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4e36" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Aminopeptidase\|Aminopeptidase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:13, 4 August 2016

2016-08-04T16:13:44Z

← Older revision		Revision as of 16:13, 4 August 2016
Line 1:		Line 1:

	==Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2 variant N392K==		==Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2 variant N392K==
	<StructureSection load='4e36' size='340' side='right' caption='[[4e36]], [[Resolution\|resolution]] 3.22Å' scene=''>		<StructureSection load='4e36' size='340' side='right' caption='[[4e36]], [[Resolution\|resolution]] 3.22Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e36]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E36 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e36]] 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=4E36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E36 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3se6\|3se6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3se6\|3se6]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERAP2, Irap, LRAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERAP2, Irap, LRAP ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e36 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e36 RCSB], [http://www.ebi.ac.uk/pdbsum/4e36 PDBsum]</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=4e36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e36 OCA], [http://pdbe.org/4e36 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e36 RCSB], [http://www.ebi.ac.uk/pdbsum/4e36 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e36 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4e36" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Birtley, J R]]		[[Category: Birtley, J R]]
	[[Category: Mavridis, I M]]		[[Category: Mavridis, I M]]

OCA at 16:53, 24 December 2014

2014-12-24T16:53:53Z

← Older revision		Revision as of 16:53, 24 December 2014
Line 1:		Line 1:
	[[~~Image~~:~~4e36~~.~~png~~\|~~left~~\|~~200px~~]]		==Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2 variant N392K==
			<StructureSection load='4e36' size='340' side='right' caption='[[4e36]], [[Resolution\|resolution]] 3.22Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4e36]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E36 FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3se6\|3se6]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERAP2, Irap, LRAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4e36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e36 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e36 RCSB], [http://www.ebi.ac.uk/pdbsum/4e36 PDBsum]</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>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2) cooperate to trim antigenic peptide precursors for loading onto MHC class I molecules and help regulate the adaptive immune response. Common coding single nucleotide polymorphisms in ERAP1 and ERAP2 have been linked with predisposition to human diseases ranging from viral and bacterial infections to autoimmunity and cancer. It has been hypothesized that altered Ag processing by these enzymes is a causal link to disease etiology, but the molecular mechanisms are obscure. We report in this article that the common ERAP2 single nucleotide polymorphism rs2549782 that codes for amino acid variation N392K leads to alterations in both the activity and the specificity of the enzyme. Specifically, the 392N allele excises hydrophobic N-terminal residues from epitope precursors up to 165-fold faster compared with the 392K allele, although both alleles are very similar in excising positively charged N-terminal amino acids. These effects are primarily due to changes in the catalytic turnover rate (k(cat)) and not in the affinity for the substrate. X-ray crystallographic analysis of the ERAP2 392K allele suggests that the polymorphism interferes with the stabilization of the N terminus of the peptide both directly and indirectly through interactions with key residues participating in catalysis. This specificity switch allows the 392N allele of ERAP2 to supplement ERAP1 activity for the removal of hydrophobic N-terminal residues. Our results provide mechanistic insight to the association of this ERAP2 polymorphism with disease and support the idea that polymorphic variation in Ag processing enzymes constitutes a component of immune response variability in humans.

	~~{{STRUCTURE_4e36\| PDB=4e36 \| SCENE= }}~~		A common single nucleotide polymorphism in endoplasmic reticulum aminopeptidase 2 induces a specificity switch that leads to altered antigen processing.,Evnouchidou I, Birtley J, Seregin S, Papakyriakou A, Zervoudi E, Samiotaki M, Panayotou G, Giastas P, Petrakis O, Georgiadis D, Amalfitano A, Saridakis E, Mavridis IM, Stratikos E J Immunol. 2012 Sep 1;189(5):2383-92. Epub 2012 Jul 25. PMID:22837489<ref>PMID:22837489</ref>

	~~===Crystal structure~~ of the ~~human Endoplasmic Reticulum Aminopeptidase 2 variant N392K===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	~~{{ABSTRACT_PUBMED_22837489}}~~		==See Also==
			*[[Aminopeptidase\|Aminopeptidase]]
	==~~About this Structure~~==		== References ==
	[[~~4e36]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens~~]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E36 OCA~~].		<references/>
			__TOC__
	==~~Reference~~==		</StructureSection>
	<~~ref group="xtra">PMID:022837489<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Birtley, J R.]]		[[Category: Birtley, J R]]
	[[Category: Mavridis, I M.]]		[[Category: Mavridis, I M]]
	[[Category: Pegias, P.]]		[[Category: Pegias, P]]
	[[Category: Saridakis, E.]]		[[Category: Saridakis, E]]
	[[Category: Stratikos, E.]]		[[Category: Stratikos, E]]
	[[Category: Aminopeptidase]]		[[Category: Aminopeptidase]]
	[[Category: Endoplasmic reticulum]]		[[Category: Endoplasmic reticulum]]

OCA at 05:54, 17 October 2012

2012-10-17T05:54:48Z

← Older revision		Revision as of 05:54, 17 October 2012
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	[[Image:4e36.~~jpg~~\|left\|200px]]		[[Image:4e36.png\|left\|200px]]

	{{STRUCTURE_4e36\| PDB=4e36 \| SCENE= }}		{{STRUCTURE_4e36\| PDB=4e36 \| SCENE= }}

OCA at 05:06, 29 August 2012

2012-08-29T05:06:00Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4e36.jpg|left|200px]]
-The entry 4e36 is ON HOLD  until Paper Publication
+{{STRUCTURE_4e36|  PDB=4e36  |  SCENE=  }}
-Authors: Birtley, J.R., Saridakis, E., Pegias, P., Stratikos, E., Mavridis, I.M.
+===Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2 variant N392K===
-Description: Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2 variant N392K
+{{ABSTRACT_PUBMED_22837489}}

OCA at 06:38, 11 April 2012

2012-04-11T06:38:24Z

← Older revision		Revision as of 06:38, 11 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4e36 is ON HOLD		The entry 4e36 is ON HOLD until Paper Publication

	Authors: Birtley, J.R., Saridakis, E., Pegias, P., Stratikos, E., Mavridis, I.M.		Authors: Birtley, J.R., Saridakis, E., Pegias, P., Stratikos, E., Mavridis, I.M.

	Description: Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2 variant N392K		Description: Crystal structure of the human Endoplasmic Reticulum Aminopeptidase 2 variant N392K

OCA: Protected "4e36" [edit=sysop:move=sysop]

2012-03-21T07:15:32Z

Protected "4e36" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:15, 21 March 2012
(No difference)