6ooz
From Proteopedia
(Difference between revisions)
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<table><tr><td colspan='2'>[[6ooz]] 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=6OOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OOZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ooz]] 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=6OOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OOZ 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]] 2.8Å</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]] 2.8Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A6Y:(S)- | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A6Y:(~{S})-[1-[(2,5-dimethylphenyl)methyl]benzimidazol-2-yl]-pyridin-4-yl-methanol'>A6Y</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6ooz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ooz OCA], [https://pdbe.org/6ooz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ooz RCSB], [https://www.ebi.ac.uk/pdbsum/6ooz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ooz 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=6ooz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ooz OCA], [https://pdbe.org/6ooz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ooz RCSB], [https://www.ebi.ac.uk/pdbsum/6ooz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ooz 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 == | ||
| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ooz" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Asymmetric hTNF-alpha
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