7kpb - Revision history

OCA at 07:17, 3 April 2024

2024-04-03T07:17:44Z

←Older revision		Revision as of 07:17, 3 April 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7kpb]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KPB FirstGlance]. <br>		<table><tr><td colspan='2'>[[7kpb]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KPB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D84:5-(1-{[2-(difluoromethoxy)phenyl]methyl}-2-{[3-(2-oxopyrrolidin-1-yl)phenoxy]methyl}-1H-benzimidazol-6-yl)pyridin-2(1H)-one'>D84</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D84:5-(1-{[2-(difluoromethoxy)phenyl]methyl}-2-{[3-(2-oxopyrrolidin-1-yl)phenoxy]methyl}-1H-benzimidazol-6-yl)pyridin-2(1H)-one'>D84</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7kpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpb OCA], [https://pdbe.org/7kpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kpb RCSB], [https://www.ebi.ac.uk/pdbsum/7kpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpb 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=7kpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpb OCA], [https://pdbe.org/7kpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kpb RCSB], [https://www.ebi.ac.uk/pdbsum/7kpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpb ProSAT]</span></td></tr>
	</table>		</table>
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	== Function ==		== Function ==
	[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>		[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 ==
-	We have recently described the development of a series of small-molecule inhibitors of human tumour necrosis factor (TNF) that stabilise an open, asymmetric, signalling-deficient form of the soluble TNF trimer. Here, we describe the generation, characterisation, and utility of a monoclonal antibody that selectively binds with high affinity to the asymmetric TNF trimer-small molecule complex. The antibody helps to define the molecular dynamics of the apo TNF trimer, reveals the mode of action and specificity of the small molecule inhibitors, acts as a chaperone in solving the human TNF-TNFR1 complex crystal structure, and facilitates the measurement of small molecule target occupancy in complex biological samples. We believe this work defines a role for monoclonal antibodies as tools to facilitate the discovery and development of small-molecule inhibitors of protein-protein interactions.
-
-	A conformation-selective monoclonal antibody against a small molecule-stabilised signalling-deficient form of TNF.,Lightwood DJ, Munro RJ, Porter J, McMillan D, Carrington B, Turner A, Scott-Tucker A, Hickford ES, Schmidt A, Fox D 3rd, Maloney A, Ceska T, Bourne T, O'Connell J, Lawson ADG Nat Commun. 2021 Jan 25;12(1):583. doi: 10.1038/s41467-020-20825-6. PMID:33495445<ref>PMID:33495445</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 7kpb" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Antibody 3D structures\|Antibody 3D structures]]		*[[Antibody 3D structures\|Antibody 3D structures]]
	*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]		*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]
-	*[[Tumor necrosis factor\|Tumor necrosis factor]]	+	*[[Tumor necrosis factor 3D structures\|Tumor necrosis factor 3D structures]]
	*[[Tumor necrosis factor receptor 3D structures\|Tumor necrosis factor receptor 3D structures]]		*[[Tumor necrosis factor receptor 3D structures\|Tumor necrosis factor receptor 3D structures]]
	== References ==		== References ==

OCA at 04:11, 25 May 2023

2023-05-25T04:11:22Z

←Older revision		Revision as of 04:11, 25 May 2023
Line 1:		Line 1:

-	====	+	==Human TNF-alpha TNFR1 complex bound to conformationally selective antibody==
-	<StructureSection load='7kpb' size='340' side='right'caption='[[7kpb]]' scene=''>	+	<StructureSection load='7kpb' size='340' side='right'caption='[[7kpb]], [[Resolution\|resolution]] 3.00Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kpb]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KPB 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=7kpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpb OCA], [https://pdbe.org/7kpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kpb RCSB], [https://www.ebi.ac.uk/pdbsum/7kpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpb ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D84:5-(1-{[2-(difluoromethoxy)phenyl]methyl}-2-{[3-(2-oxopyrrolidin-1-yl)phenoxy]methyl}-1H-benzimidazol-6-yl)pyridin-2(1H)-one'>D84</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7kpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpb OCA], [https://pdbe.org/7kpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kpb RCSB], [https://www.ebi.ac.uk/pdbsum/7kpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpb ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[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 ==
		+	[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 ==
		+	We have recently described the development of a series of small-molecule inhibitors of human tumour necrosis factor (TNF) that stabilise an open, asymmetric, signalling-deficient form of the soluble TNF trimer. Here, we describe the generation, characterisation, and utility of a monoclonal antibody that selectively binds with high affinity to the asymmetric TNF trimer-small molecule complex. The antibody helps to define the molecular dynamics of the apo TNF trimer, reveals the mode of action and specificity of the small molecule inhibitors, acts as a chaperone in solving the human TNF-TNFR1 complex crystal structure, and facilitates the measurement of small molecule target occupancy in complex biological samples. We believe this work defines a role for monoclonal antibodies as tools to facilitate the discovery and development of small-molecule inhibitors of protein-protein interactions.
		+
		+	A conformation-selective monoclonal antibody against a small molecule-stabilised signalling-deficient form of TNF.,Lightwood DJ, Munro RJ, Porter J, McMillan D, Carrington B, Turner A, Scott-Tucker A, Hickford ES, Schmidt A, Fox D 3rd, Maloney A, Ceska T, Bourne T, O'Connell J, Lawson ADG Nat Commun. 2021 Jan 25;12(1):583. doi: 10.1038/s41467-020-20825-6. PMID:33495445<ref>PMID:33495445</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kpb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]
		+	*[[Tumor necrosis factor\|Tumor necrosis factor]]
		+	*[[Tumor necrosis factor receptor 3D structures\|Tumor necrosis factor receptor 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Mus musculus]]
		+	[[Category: Ceska T]]
		+	[[Category: Conrady DG]]
		+	[[Category: Fox III D]]
		+	[[Category: Lowe M]]

OCA at 11:18, 3 February 2021

2021-02-03T11:18:06Z

←Older revision		Revision as of 11:18, 3 February 2021
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	<StructureSection load='7kpb' size='340' side='right'caption='[[7kpb]]' scene=''>		<StructureSection load='7kpb' size='340' side='right'caption='[[7kpb]]' 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= OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	</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=7kpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpb OCA], [~~http~~://pdbe.org/7kpb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7kpb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7kpb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpb ProSAT]</span></td></tr>	+	</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=7kpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpb OCA], [https://pdbe.org/7kpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kpb RCSB], [https://www.ebi.ac.uk/pdbsum/7kpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpb ProSAT]</span></td></tr>
	</table>		</table>
	__TOC__		__TOC__

OCA at 05:56, 20 January 2021

2021-01-20T05:56:44Z

←Older revision		Revision as of 05:56, 20 January 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7kpb ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7kpb' size='340' side='right'caption='[[7kpb]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7kpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kpb OCA], [http://pdbe.org/7kpb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7kpb RCSB], [http://www.ebi.ac.uk/pdbsum/7kpb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7kpb ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 05:32, 25 November 2020

2020-11-25T05:32:03Z

←Older revision		Revision as of 05:32, 25 November 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7kpb is ON HOLD	+	The entry 7kpb is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7kpb" [edit=sysop:move=sysop]

2020-11-18T08:11:33Z

Protected "7kpb" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:11, 18 November 2020

OCA: New page: '''Unreleased structure''' The entry 7kpb is ON HOLD Authors: Description: Category: Unreleased Structures

2020-11-18T08:11:32Z

New page: '''Unreleased structure''' The entry 7kpb is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7kpb is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]