6ooy - Revision history

OCA at 07:07, 3 April 2024

2024-04-03T07:07:45Z

←Older revision		Revision as of 07:07, 3 April 2024
Line 3:		Line 3:
	<StructureSection load='6ooy' size='340' side='right'caption='[[6ooy]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='6ooy' size='340' side='right'caption='[[6ooy]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ooy]] is a 3 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=6OOY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6OOY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ooy]] is a 3 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=6OOY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OOY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A7M:{1-[(2,5-dimethylphenyl)methyl]-1H-benzimidazol-2-yl}methanol'>A7M</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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]] 2.5Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNF, TNFA, TNFSF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A7M:{1-[(2,5-dimethylphenyl)methyl]-1H-benzimidazol-2-yl}methanol'>A7M</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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=6ooy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ooy OCA], [~~http~~://pdbe.org/6ooy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6ooy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6ooy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6ooy 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=6ooy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ooy OCA], [https://pdbe.org/6ooy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ooy RCSB], [https://www.ebi.ac.uk/pdbsum/6ooy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ooy ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:[~~http~~://omim.org/entry/607507 607507]]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).	+	[https://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN] Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:[https://omim.org/entry/607507 607507]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.<ref>PMID:16829952</ref> The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.<ref>PMID:16829952</ref>	+	[https://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.<ref>PMID:16829952</ref> The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.<ref>PMID:16829952</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Tumour necrosis factor (TNF) is a cytokine belonging to a family of trimeric proteins; it has been shown to be a key mediator in autoimmune diseases such as rheumatoid arthritis and Crohn's disease. While TNF is the target of several successful biologic drugs, attempts to design small molecule therapies directed to this cytokine have not led to approved products. Here we report the discovery of potent small molecule inhibitors of TNF that stabilise an asymmetrical form of the soluble TNF trimer, compromising signalling and inhibiting the functions of TNF in vitro and in vivo. This discovery paves the way for a class of small molecule drugs capable of modulating TNF function by stabilising a naturally sampled, receptor-incompetent conformation of TNF. Furthermore, this approach may prove to be a more general mechanism for inhibiting protein-protein interactions.	+

-	Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer.,O'Connell J, Porter J, Kroeplien B, Norman T, Rapecki S, Davis R, McMillan D, Arakaki T, Burgin A, Fox Iii D, Ceska T, Lecomte F, Maloney A, Vugler A, Carrington B, Cossins BP, Bourne T, Lawson A Nat Commun. 2019 Dec 19;10(1):5795. doi: 10.1038/s41467-019-13616-1. PMID:31857588<ref>PMID:31857588</ref>	+	==See Also==
-		+	*[[Tumor necrosis factor 3D structures\|Tumor necrosis factor 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 6ooy" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Arakaki~~, T L~~]]	+	[[Category: Arakaki TL]]
-	[[Category: Ceska, T]]	+	[[Category: Ceska T]]
-	[[Category: Edwards~~, T E]]~~	+	[[Category: Edwards TE]]
-	~~[[Category: Asymmetric]]~~	+
-	~~[[Category: Cytokine]]~~	+
-	~~[[Category: Protein-protein interaction inhibitor]]~~	+
-	~~[[Category: Rheumatoid arthritis]]~~	+
-	~~[[Category: Tnf]]~~	+
-	~~[[Category: Tumour necrosis factor alpha~~]]	+

OCA at 11:55, 1 January 2020

2020-01-01T11:55:11Z

←Older revision		Revision as of 11:55, 1 January 2020
Line 3:		Line 3:
	<StructureSection load='6ooy' size='340' side='right'caption='[[6ooy]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='6ooy' size='340' side='right'caption='[[6ooy]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ooy]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OOY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OOY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ooy]] is a 3 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=6OOY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OOY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A7M:{1-[(2,5-dimethylphenyl)methyl]-1H-benzimidazol-2-yl}methanol'>A7M</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A7M:{1-[(2,5-dimethylphenyl)methyl]-1H-benzimidazol-2-yl}methanol'>A7M</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNF, TNFA, TNFSF2 ([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=6ooy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ooy OCA], [http://pdbe.org/6ooy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ooy RCSB], [http://www.ebi.ac.uk/pdbsum/6ooy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ooy ProSAT]</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=6ooy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ooy OCA], [http://pdbe.org/6ooy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ooy RCSB], [http://www.ebi.ac.uk/pdbsum/6ooy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ooy ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.<ref>PMID:16829952</ref> The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.<ref>PMID:16829952</ref>		[[http://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.<ref>PMID:16829952</ref> The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.<ref>PMID:16829952</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tumour necrosis factor (TNF) is a cytokine belonging to a family of trimeric proteins; it has been shown to be a key mediator in autoimmune diseases such as rheumatoid arthritis and Crohn's disease. While TNF is the target of several successful biologic drugs, attempts to design small molecule therapies directed to this cytokine have not led to approved products. Here we report the discovery of potent small molecule inhibitors of TNF that stabilise an asymmetrical form of the soluble TNF trimer, compromising signalling and inhibiting the functions of TNF in vitro and in vivo. This discovery paves the way for a class of small molecule drugs capable of modulating TNF function by stabilising a naturally sampled, receptor-incompetent conformation of TNF. Furthermore, this approach may prove to be a more general mechanism for inhibiting protein-protein interactions.
		+
		+	Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer.,O'Connell J, Porter J, Kroeplien B, Norman T, Rapecki S, Davis R, McMillan D, Arakaki T, Burgin A, Fox Iii D, Ceska T, Lecomte F, Maloney A, Vugler A, Carrington B, Cossins BP, Bourne T, Lawson A Nat Commun. 2019 Dec 19;10(1):5795. doi: 10.1038/s41467-019-13616-1. PMID:31857588<ref>PMID:31857588</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6ooy" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Arakaki, T L]]		[[Category: Arakaki, T L]]

OCA at 09:09, 25 December 2019

2019-12-25T09:09:33Z

←Older revision		Revision as of 09:09, 25 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ooy is ~~ON HOLD until Paper Publication~~	+	==Asymmetric hTNF-alpha==
-		+	<StructureSection load='6ooy' size='340' side='right'caption='[[6ooy]], [[Resolution\|resolution]] 2.50Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6ooy]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OOY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OOY FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A7M:{1-[(2,5-dimethylphenyl)methyl]-1H-benzimidazol-2-yl}methanol'>A7M</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6ooy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ooy OCA], [http://pdbe.org/6ooy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ooy RCSB], [http://www.ebi.ac.uk/pdbsum/6ooy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ooy ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:[http://omim.org/entry/607507 607507]]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.<ref>PMID:16829952</ref> The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.<ref>PMID:16829952</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Arakaki, T L]]
		+	[[Category: Ceska, T]]
		+	[[Category: Edwards, T E]]
		+	[[Category: Asymmetric]]
		+	[[Category: Cytokine]]
		+	[[Category: Protein-protein interaction inhibitor]]
		+	[[Category: Rheumatoid arthritis]]
		+	[[Category: Tnf]]
		+	[[Category: Tumour necrosis factor alpha]]

OCA at 21:05, 5 June 2019

2019-06-05T21:05:34Z

←Older revision		Revision as of 21:05, 5 June 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

2019-05-01T07:15:48Z

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

←Older revision

Revision as of 07:15, 1 May 2019

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

2019-05-01T07:15:46Z

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

New page

'''Unreleased structure'''

The entry 6ooy is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]