View source for 5mu8


==HUMAN TNF-ALPHA IN COMPLEX WITH JNJ525==
<StructureSection load='5mu8' size='340' side='right'caption='[[5mu8]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mu8]] is a 48 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=5MU8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MU8 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]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JNI:~{N}4-(PHENYLMETHYL)-~{N}4-[2-[3-(2-PIPERAZIN-1-YLPYRIMIDIN-5-YL)PHENYL]PHENYL]PYRIMIDINE-2,4-DIAMINE'>JNI</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=5mu8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mu8 OCA], [https://pdbe.org/5mu8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mu8 RCSB], [https://www.ebi.ac.uk/pdbsum/5mu8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mu8 ProSAT]</span></td></tr>
</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 ==
A prevalent observation in high-throughput screening and drug discovery programs is the inhibition of protein function by small-molecule compound aggregation. Here, we present the X-ray structural description of aggregation-based inhibition of a protein-protein interaction involving tumor necrosis factor alpha (TNFalpha). An ordered conglomerate of an aggregating small-molecule inhibitor (JNJ525) induces a quaternary structure switch of TNFalpha that inhibits the protein-protein interaction between TNFalpha and TNFalpha receptors. SPD-304 may employ a similar mechanism of inhibition.

Structural Basis of Small-Molecule Aggregate Induced Inhibition of a Protein-Protein Interaction.,Blevitt JM, Hack MD, Herman KL, Jackson PF, Krawczuk PJ, Lebsack AD, Liu AX, Mirzadegan T, Nelen MI, Patrick AN, Steinbacher S, Milla ME, Lumb KJ J Med Chem. 2017 Mar 16. PMID:28300404<ref>PMID:28300404</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mu8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tumor necrosis factor|Tumor necrosis factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Blevitt JM]]
[[Category: Hack MD]]
[[Category: Herman KL]]
[[Category: Jackson PF]]
[[Category: Krawczuk PJ]]
[[Category: Lebsack AD]]
[[Category: Liu AX]]
[[Category: Lumb KJ]]
[[Category: Milla ME]]
[[Category: Mirzadegan T]]
[[Category: Nelen MI]]
[[Category: Patrick AP]]
[[Category: Steinbacher S]]