7kpb
From Proteopedia
(Difference between revisions)
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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. | ||
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| - | 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> | ||
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| - | 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 == | ||
Revision as of 07:17, 3 April 2024
Human TNF-alpha TNFR1 complex bound to conformationally selective antibody
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