3wd5
From Proteopedia
(Difference between revisions)
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<StructureSection load='3wd5' size='340' side='right' caption='[[3wd5]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='3wd5' size='340' side='right' caption='[[3wd5]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3wd5]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[3wd5]] 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=3WD5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WD5 FirstGlance]. <br> |
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g3y|4g3y]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g3y|4g3y]]</td></tr> | ||
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFA ([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=3wd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wd5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wd5 RCSB], [http://www.ebi.ac.uk/pdbsum/3wd5 PDBsum]</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=3wd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wd5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wd5 RCSB], [http://www.ebi.ac.uk/pdbsum/3wd5 PDBsum]</span></td></tr> | ||
</table> | </table> | ||
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== 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 == | ||
| + | TNFalpha-targeting therapy with the use of the drugs Etanercept, Infliximab, and Adalimumab is used in the clinical treatment of various inflammatory and immune diseases. Although all of these reagents function to disrupt the interaction between TNFalpha and its receptors, clinical investigations showed the advantages of Adalimumab treatment compared with Etanercept and Infliximab. However, the underlying molecular mechanism of action of Adalimumab remains unclear. In our previous work, we presented structural data on how Infliximab binds with the E-F loop of TNFalpha and functions as a TNFalpha receptor-binding blocker. To further elucidate the variations between TNFalpha inhibitors, we solved the crystal structure of TNFalpha in complex with Adalimumab Fab. The structural observation and the mutagenesis analysis provided direct evidence for identifying the Adalimumab epitope on TNFalpha and revealed the mechanism of Adalimumab inhibition of TNFalpha by occupying the TNFalpha receptor-binding site. The larger antigen-antibody interface in TNFalpha Adalimumab also provided information at a molecular level for further understanding the clinical advantages of Adalimumab therapy compared with Infliximab. | ||
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| + | Comparison of the inhibition mechanisms of adalimumab and infliximab in treating tumor necrosis factor alpha-associated diseases from a molecular view.,Hu S, Liang S, Guo H, Zhang D, Li H, Wang X, Yang W, Qian W, Hou S, Wang H, Guo Y, Lou Z J Biol Chem. 2013 Sep 20;288(38):27059-67. doi: 10.1074/jbc.M113.491530. Epub, 2013 Aug 13. PMID:23943614<ref>PMID:23943614</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Human]] |
[[Category: Guo, Y J]] | [[Category: Guo, Y J]] | ||
[[Category: Hu, S]] | [[Category: Hu, S]] | ||
Revision as of 12:07, 1 July 2015
Crystal structure of TNFalpha in complex with Adalimumab Fab fragment
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