8ea6 - Revision history

OCA at 09:34, 17 October 2024

2024-10-17T09:34:56Z

← Older revision		Revision as of 09:34, 17 October 2024
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	<table><tr><td colspan='2'>[[8ea6]] 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=8EA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EA6 FirstGlance]. <br>		<table><tr><td colspan='2'>[[8ea6]] 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=8EA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EA6 FirstGlance]. <br>
	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.73Å</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]] 1.73Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VMB:N-{~~(1S~~)-2-(dimethylamino)-2-~~oxo~~-1-[3-(trifluoromethyl)phenyl]ethyl}-4-(trifluoromethyl)~~[1,1-biphenyl~~]~~-2-carboxamide~~'>VMB</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VMB:~{N}-[(1~{S})-2-(dimethylamino)-2-oxidanylidene-1-[3-(trifluoromethyl)phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide'>VMB</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=8ea6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ea6 OCA], [https://pdbe.org/8ea6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ea6 RCSB], [https://www.ebi.ac.uk/pdbsum/8ea6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ea6 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=8ea6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ea6 OCA], [https://pdbe.org/8ea6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ea6 RCSB], [https://www.ebi.ac.uk/pdbsum/8ea6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ea6 ProSAT]</span></td></tr>
	</table>		</table>
	== ~~Function~~ ==		<div style="background-color:#fffaf0;">
	~~[https://www.uniprot.org/uniprot/NKG2D_HUMAN NKG2D_HUMAN] Receptor for MICA~~, ~~MICB~~, ~~ULBP1~~, ~~ULBP2, ULBP3~~ (~~ULBP2>ULBP1>ULBP3~~) and ~~ULBP4~~. ~~Plays a role~~ as a ~~receptor for~~ the ~~recognition~~ of ~~MHC class I HLA-E molecules~~ by ~~NK cells~~ and ~~some cytotoxic T~~-~~cells~~. ~~Involved in~~ the ~~immune surveillance exerted by T~~- ~~and B~~-~~lymphocytes~~.		== Publication Abstract from PubMed ==
			NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, gammadelta(+), and CD8(+) T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein-protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2D dimer to open apart and twist relative to one another. Leveraging a suite of biochemical and cell-based assays coupled with structure-based drug design, we established tractable structure-activity relationships with one of the chemical series and successfully improved both the potency and physicochemical properties. Together, we demonstrate that it is possible, albeit challenging, to disrupt the interaction between NKG2D and multiple protein ligands with a single molecule through allosteric modulation of the NKG2D receptor dimer/ligand interface.

			Identification of small-molecule protein-protein interaction inhibitors for NKG2D.,Thompson AA, Harbut MB, Kung PP, Karpowich NK, Branson JD, Grant JC, Hagan D, Pascual HA, Bai G, Zavareh RB, Coate HR, Collins BC, Cote M, Gelin CF, Damm-Ganamet KL, Gholami H, Huff AR, Limon L, Lumb KJ, Mak PA, Nakafuku KM, Price EV, Shih AY, Tootoonchi M, Vellore NA, Wang J, Wei N, Ziff J, Berger SB, Edwards JP, Gardet A, Sun S, Towne JE, Venable JD, Shi Z, Venkatesan H, Rives ML, Sharma S, Shireman BT, Allen SJ Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2216342120. doi: , 10.1073/pnas.2216342120. Epub 2023 Apr 25. PMID:37098070<ref>PMID:37098070</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 8ea6" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[NK cell receptor\|NK cell receptor]]		*[[NK cell receptor\|NK cell receptor]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 10:19, 25 October 2023

2023-10-25T10:19:53Z

← Older revision		Revision as of 10:19, 25 October 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8ea6]] 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=8EA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EA6 FirstGlance]. <br>		<table><tr><td colspan='2'>[[8ea6]] 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=8EA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EA6 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VMB:N-{(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl}-4-(trifluoromethyl)[1,1-biphenyl]-2-carboxamide'>VMB</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]] 1.73Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VMB:N-{(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl}-4-(trifluoromethyl)[1,1-biphenyl]-2-carboxamide'>VMB</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=8ea6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ea6 OCA], [https://pdbe.org/8ea6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ea6 RCSB], [https://www.ebi.ac.uk/pdbsum/8ea6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ea6 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=8ea6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ea6 OCA], [https://pdbe.org/8ea6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ea6 RCSB], [https://www.ebi.ac.uk/pdbsum/8ea6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ea6 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/NKG2D_HUMAN NKG2D_HUMAN] Receptor for MICA, MICB, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. Involved in the immune surveillance exerted by T- and B-lymphocytes.		[https://www.uniprot.org/uniprot/NKG2D_HUMAN NKG2D_HUMAN] Receptor for MICA, MICB, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. Involved in the immune surveillance exerted by T- and B-lymphocytes.

			==See Also==
			*[[NK cell receptor\|NK cell receptor]]
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:30, 3 May 2023

2023-05-03T07:30:39Z

← Older revision		Revision as of 07:30, 3 May 2023
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 8ea6 is ~~ON HOLD~~		==NKG2D complexed with inhibitor 3e==
			<StructureSection load='8ea6' size='340' side='right'caption='[[8ea6]], [[Resolution\|resolution]] 1.73Å' scene=''>
	~~Authors~~:		== Structural highlights ==
			<table><tr><td colspan='2'>[[8ea6]] 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=8EA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EA6 FirstGlance]. <br>
	~~Description~~:		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VMB:N-{(1S)-2-(dimethylamino)-2-oxo-1-[3-(trifluoromethyl)phenyl]ethyl}-4-(trifluoromethyl)[1,1-biphenyl]-2-carboxamide'>VMB</scene></td></tr>
	[[Category: ~~Unreleased~~ Structures]]		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ea6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ea6 OCA], [https://pdbe.org/8ea6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ea6 RCSB], [https://www.ebi.ac.uk/pdbsum/8ea6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ea6 ProSAT]</span></td></tr>
			</table>
			== Function ==
			[https://www.uniprot.org/uniprot/NKG2D_HUMAN NKG2D_HUMAN] Receptor for MICA, MICB, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. Involved in the immune surveillance exerted by T- and B-lymphocytes.
			__TOC__
			</StructureSection>
			[[Category: Homo sapiens]]
			[[Category: Large Structures]]
			[[Category: Grant JC]]
			[[Category: Karpowich NK]]
			[[Category: Sharma S]]
			[[Category: Thompson AA]]

OCA: Protected "8ea6" [edit=sysop:move=sysop]

2022-09-07T15:35:16Z

Protected "8ea6" [edit=sysop:move=sysop]

← Older revision	Revision as of 15:35, 7 September 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8ea6 is ON HOLD Authors: Description: Category: Unreleased Structures

2022-09-07T15:35:15Z

New page: '''Unreleased structure''' The entry 8ea6 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8ea6 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]