7ta6
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7ta6]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TA6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ta6]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TA6 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=XCP:(1S,2S)-2-AMINOCYCLOPENTANECARBOXYLIC+ACID'>XCP</scene>, <scene name='pdbligand=XPC:(3S,4R)-4-AMINOPYRROLIDINE-3-CARBOXYLIC+ACID'>XPC</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]] 2.67Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=XCP:(1S,2S)-2-AMINOCYCLOPENTANECARBOXYLIC+ACID'>XCP</scene>, <scene name='pdbligand=XPC:(3S,4R)-4-AMINOPYRROLIDINE-3-CARBOXYLIC+ACID'>XPC</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=7ta6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ta6 OCA], [https://pdbe.org/7ta6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ta6 RCSB], [https://www.ebi.ac.uk/pdbsum/7ta6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ta6 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=7ta6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ta6 OCA], [https://pdbe.org/7ta6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ta6 RCSB], [https://www.ebi.ac.uk/pdbsum/7ta6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ta6 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 == | ||
| - | Aberrant tumor necrosis factor-alpha (TNFalpha) signaling is associated with many inflammatory diseases. The homotrimeric quaternary structure of TNFalpha is essential for receptor recognition and signal transduction. Previously, we described an engineered alpha/beta-peptide inhibitor that potently suppresses TNFalpha activity and resists proteolysis. Here, we present structural evidence that both the alpha/beta-peptide inhibitor and an all-alpha analogue bind to a monomeric form of TNFalpha. Calorimetry data support a 1:1 inhibitor/TNFalpha stoichiometry in solution. In contrast, previous cocrystal structures involving peptide or small-molecule inhibitors have shown the antagonists engaging a TNFalpha dimer. The structural data reveal why our inhibitors favor monomeric TNFalpha. Previous efforts to block TNFalpha-induced cell death with peptide inhibitors revealed that surfactant additives to the assay conditions cause a more rapid manifestation of inhibitory activity than is observed in the absence of additives. We attributed this effect to a loose surfactant TNFalpha association that lowers the barrier to trimer dissociation. Here, we used the new structural data to design peptide inhibitors bearing a surfactant-inspired appendage intended to facilitate TNFalpha trimer dissociation. The appendage modified the time course of protection from cell death. | ||
| - | + | ==See Also== | |
| - | + | *[[Tumor necrosis factor 3D structures|Tumor necrosis factor 3D structures]] | |
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== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Trimer-to-Monomer Disruption of Tumor Necrosis Factor-alpha (TNF-alpha) by unnatural alpha/beta-peptide-1
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