6t6r - Revision history

OCA at 07:24, 8 April 2020

OCA — Wed, 08 Apr 2020 07:24:14 GMT

←Older revision		Revision as of 07:24, 8 April 2020
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	<StructureSection load='6t6r' size='340' side='right'caption='[[6t6r]], [[Resolution\|resolution]] 1.67Å' scene=''>		<StructureSection load='6t6r' size='340' side='right'caption='[[6t6r]], [[Resolution\|resolution]] 1.67Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6t6r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T6R OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6T6R FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6t6r]] is a 1 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=6T6R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6T6R FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=MNZ:(4~{a}~{R},5~{S},6~{R},8~{S},8~{a}~{R})-5-[2-(furan-3-yl)ethyl]-5,6,8~{a}-trimethyl-8-oxidanyl-3,4,4~{a},6,7,8-hexahydronaphthalene-1-carboxylic+acid'>MNZ</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=MNZ:(4~{a}~{R},5~{S},6~{R},8~{S},8~{a}~{R})-5-[2-(furan-3-yl)ethyl]-5,6,8~{a}-trimethyl-8-oxidanyl-3,4,4~{a},6,7,8-hexahydronaphthalene-1-carboxylic+acid'>MNZ</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'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6t6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t6r OCA], [http://pdbe.org/6t6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t6r RCSB], [http://www.ebi.ac.uk/pdbsum/6t6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t6r ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERAP1, APPILS, ARTS1, KIAA0525, UNQ584/PRO1154 ([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://proteopedia.org/fgij/fg.htm?mol=6t6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t6r OCA], [http://pdbe.org/6t6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t6r RCSB], [http://www.ebi.ac.uk/pdbsum/6t6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t6r ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Rowland, P]]		[[Category: Rowland, P]]

OCA at 09:52, 18 March 2020

OCA — Wed, 18 Mar 2020 09:52:55 GMT

←Older revision		Revision as of 09:52, 18 March 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6t6r is ~~ON HOLD~~	+	==Human endoplasmic reticulum aminopeptidase 1 (ERAP1) in complex with (4aR,5S,6R,8S,8aR)-5-(2-(Furan-3-yl)ethyl)-8-hydroxy-5,6,8a-trimethyl-3,4,4a,5,6,7,8,8a-octahydronaphthalene-1-carboxylic acid==
		+	<StructureSection load='6t6r' size='340' side='right'caption='[[6t6r]], [[Resolution\|resolution]] 1.67Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6t6r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6T6R FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=MNZ:(4~{a}~{R},5~{S},6~{R},8~{S},8~{a}~{R})-5-[2-(furan-3-yl)ethyl]-5,6,8~{a}-trimethyl-8-oxidanyl-3,4,4~{a},6,7,8-hexahydronaphthalene-1-carboxylic+acid'>MNZ</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6t6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t6r OCA], [http://pdbe.org/6t6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t6r RCSB], [http://www.ebi.ac.uk/pdbsum/6t6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t6r ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ERAP1_HUMAN ERAP1_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. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney.<ref>PMID:15908954</ref> <ref>PMID:16286653</ref> <ref>PMID:21478864</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	ER aminopeptidase 1 (ERAP1) is an intracellular enzyme that generates antigenic peptides and is an emerging target for cancer immunotherapy and the control of autoimmunity. ERAP1 inhibitors described previously target the active site and are limited in selectivity, minimizing their clinical potential. To address this, we targeted the regulatory site of ERAP1 using a high-throughput screen and discovered a small molecule hit that is highly selective for ERAP1. (4aR,5S,6R,8S,8aR)-5-(2-(Furan-3-yl)ethyl)-8-hydroxy-5,6,8a-trimethyl-3,4,4a,5,6, 7,8,8a-octahydronaphthalene-1-carboxylic acid is a natural product found in Dodonaea viscosa that constitutes a submicromolar, highly selective, and cell-active modulator of ERAP1. Although the compound activates hydrolysis of small model substrates, it is a competitive inhibitor for physiologically relevant longer peptides. Crystallographic analysis confirmed that the compound targets the regulatory site of the enzyme that normally binds the C-terminus of the peptide substrate. Our findings constitute a novel starting point for the development of selective ERAP1 modulators that have potential for further clinical development.

-	~~Authors~~:	+	Targeting the Regulatory Site of ER Aminopeptidase 1 Leads to the Discovery of a Natural Product Modulator of Antigen Presentation.,Liddle J, Hutchinson JP, Kitchen S, Rowland P, Neu M, Cecconie T, Holmes DS, Jones E, Korczynska J, Koumantou D, Lea JD, Nickels L, Pemberton M, Phillipou A, Schneck JL, Sheehan H, Tinworth CP, Uings I, Wojno-Picon J, Young RJ, Stratikos E J Med Chem. 2020 Mar 9. doi: 10.1021/acs.jmedchem.9b02123. PMID:32109056<ref>PMID:32109056</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6t6r" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Rowland, P]]
		+	[[Category: Aminopeptidase]]
		+	[[Category: Erap1]]
		+	[[Category: Hydrolase]]

OCA: Protected "6t6r" [edit=sysop:move=sysop]

OCA — Wed, 30 Oct 2019 07:27:54 GMT

Protected "6t6r" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:27, 30 October 2019

OCA: New page: '''Unreleased structure''' The entry 6t6r is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 30 Oct 2019 07:27:53 GMT

New page: '''Unreleased structure''' The entry 6t6r is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6t6r is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]