6wml - Revision history

OCA at 14:30, 18 October 2023

2023-10-18T14:30:47Z

←Older revision		Revision as of 14:30, 18 October 2023
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	==Human TLR8 bound to the potent agonist, GS-9688 (Selgantolimod)==		==Human TLR8 bound to the potent agonist, GS-9688 (Selgantolimod)==
-	<StructureSection load='6wml' size='340' side='right'caption='[[6wml]]' scene=''>	+	<StructureSection load='6wml' size='340' side='right'caption='[[6wml]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WML OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WML FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6wml]] is a 4 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=6WML OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WML FirstGlance]. <br>
-	</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=6wml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wml OCA], [https://pdbe.org/6wml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wml RCSB], [https://www.ebi.ac.uk/pdbsum/6wml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wml ProSAT]</span></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]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=U57:(2R)-2-[(2-amino-7-fluoropyrido[3,2-d]pyrimidin-4-yl)amino]-2-methylhexan-1-ol'>U57</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=6wml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wml OCA], [https://pdbe.org/6wml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wml RCSB], [https://www.ebi.ac.uk/pdbsum/6wml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wml ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/TLR8_HUMAN TLR8_HUMAN] Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.<ref>PMID:17932028</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Toll-like receptor 8 (TLR8) recognizes pathogen-derived single-stranded RNA fragments to trigger innate and adaptive immune responses. Chronic hepatitis B (CHB) is associated with a dysfunctional immune response, and therefore a selective TLR8 agonist may be an effective treatment option. Structure-based optimization of a dual TLR7/8 agonist led to the identification of the selective TLR8 clinical candidate (R)-2-((2-amino-7-fluoropyrido[3,2-d]pyrimidin-4-yl)amino)-2-methylhexan-1-ol (GS-9688, (R)-7). Potent TLR8 agonism (IL-12p40 EC50 = 220 nM) and >100-fold TLR7 selectivity (IFN-alpha EC50 > 50 muM) was observed in human peripheral blood mononuclear cells (PBMCs). The TLR8-ectodomain:(R)-7 complex confirmed TLR8 binding and a direct ligand interaction with TLR8 residue Asp545. Oral (R)-7 had good absorption and high first pass clearance in preclinical species. A reduction in viral markers was observed in HBV-infected primary human hepatocytes treated with media from PBMCs stimulated with (R)-7, supporting the clinical development of (R)-7 for the treatment of CHB.
		+
		+	Discovery of GS-9688 (Selgantolimod) as a Potent and Selective Oral Toll-Like Receptor 8 Agonist for the Treatment of Chronic Hepatitis B.,Mackman RL, Mish M, Chin G, Perry JK, Appleby T, Aktoudianakis V, Metobo S, Pyun P, Niu C, Daffis S, Yu H, Zheng J, Villasenor AG, Zablocki J, Chamberlain J, Jin H, Lee G, Suekawa-Pirrone K, Santos R, Delaney WE 4th, Fletcher SP J Med Chem. 2020 Sep 24;63(18):10188-10203. doi: 10.1021/acs.jmedchem.0c00100., Epub 2020 Jun 3. PMID:32407112<ref>PMID:32407112</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6wml" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Toll-like Receptor 3D structures\|Toll-like Receptor 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Appleby TC]]		[[Category: Appleby TC]]

OCA at 11:07, 3 February 2021

2021-02-03T11:07:26Z

←Older revision		Revision as of 11:07, 3 February 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 6wml ~~is ON HOLD until Paper Publication~~	+	==Human TLR8 bound to the potent agonist, GS-9688 (Selgantolimod)==
-		+	<StructureSection load='6wml' size='340' side='right'caption='[[6wml]]' scene=''>
-	~~Authors~~: ~~Appleby, T~~.C., ~~Perry, J~~.K., ~~Mish~~, M., ~~Villasenor, A~~.G., ~~Mackman, R~~.L.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WML OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WML FirstGlance]. <br>
-	~~Description: Human TLR8 bound to the potent agonist, GS-9688 (Selgantolimod)~~	+	</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=6wml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wml OCA], [https://pdbe.org/6wml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wml RCSB], [https://www.ebi.ac.uk/pdbsum/6wml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wml ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Villasenor, A.G~~]]	+	__TOC__
-	[[Category: ~~Mish, M~~]]	+	</StructureSection>
-	[[Category: ~~Appleby, T.C~~]]	+	[[Category: Large Structures]]
-	[[Category: Perry~~, J.K~~]]	+	[[Category: Appleby TC]]
-	[[Category: ~~Mackman, R.L~~]]	+	[[Category: Mackman RL]]
		+	[[Category: Mish M]]
		+	[[Category: Perry JK]]
		+	[[Category: Villasenor AG]]

OCA at 06:32, 20 January 2021

2021-01-20T06:32:48Z

←Older revision		Revision as of 06:32, 20 January 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6wml is ON HOLD	+	The entry 6wml is ON HOLD until Paper Publication

	Authors: Appleby, T.C., Perry, J.K., Mish, M., Villasenor, A.G., Mackman, R.L.		Authors: Appleby, T.C., Perry, J.K., Mish, M., Villasenor, A.G., Mackman, R.L.
Line 7:		Line 7:
	Description: Human TLR8 bound to the potent agonist, GS-9688 (Selgantolimod)		Description: Human TLR8 bound to the potent agonist, GS-9688 (Selgantolimod)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Mackman, R.L]]
	[[Category: Villasenor, A.G]]		[[Category: Villasenor, A.G]]
	[[Category: Mish, M]]		[[Category: Mish, M]]
	[[Category: Appleby, T.C]]		[[Category: Appleby, T.C]]
	[[Category: Perry, J.K]]		[[Category: Perry, J.K]]
		+	[[Category: Mackman, R.L]]

OCA at 10:37, 8 July 2020

2020-07-08T10:37:40Z

←Older revision		Revision as of 10:37, 8 July 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6wml is ON HOLD ~~until sometime in the future~~	+	The entry 6wml is ON HOLD

	Authors: Appleby, T.C., Perry, J.K., Mish, M., Villasenor, A.G., Mackman, R.L.		Authors: Appleby, T.C., Perry, J.K., Mish, M., Villasenor, A.G., Mackman, R.L.
Line 8:		Line 8:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Mackman, R.L]]		[[Category: Mackman, R.L]]
-	[[Category: Appleby, T.C]]
	[[Category: Villasenor, A.G]]		[[Category: Villasenor, A.G]]
	[[Category: Mish, M]]		[[Category: Mish, M]]
		+	[[Category: Appleby, T.C]]
	[[Category: Perry, J.K]]		[[Category: Perry, J.K]]

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

2020-04-29T05:17:51Z

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

←Older revision

Revision as of 05:17, 29 April 2020

OCA: New page: '''Unreleased structure''' The entry 6wml is ON HOLD until sometime in the future Authors: Appleby, T.C., Perry, J.K., Mish, M., Villasenor, A.G., Mackman, R.L. Description: Human TLR8...

2020-04-29T05:17:49Z

New page: '''Unreleased structure''' The entry 6wml is ON HOLD until sometime in the future Authors: Appleby, T.C., Perry, J.K., Mish, M., Villasenor, A.G., Mackman, R.L. Description: Human TLR8...

New page

'''Unreleased structure'''

The entry 6wml is ON HOLD until sometime in the future

Authors: Appleby, T.C., Perry, J.K., Mish, M., Villasenor, A.G., Mackman, R.L.

Description: Human TLR8 bound to the potent agonist, GS-9688 (Selgantolimod)
[[Category: Unreleased Structures]]
[[Category: Mackman, R.L]]
[[Category: Appleby, T.C]]
[[Category: Villasenor, A.G]]
[[Category: Mish, M]]
[[Category: Perry, J.K]]