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2zpx

From Proteopedia

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{{Seed}}
 
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[[Image:2zpx.jpg|left|200px]]
 
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<!--
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==TNF Receptor Subtype One-selective TNF Mutant with Antagonistic Activity; R1antTNF-T8==
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The line below this paragraph, containing "STRUCTURE_2zpx", creates the "Structure Box" on the page.
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<StructureSection load='2zpx' size='340' side='right'caption='[[2zpx]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2zpx]] 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=2ZPX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZPX FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.83&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2zpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zpx OCA], [https://pdbe.org/2zpx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zpx RCSB], [https://www.ebi.ac.uk/pdbsum/2zpx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zpx ProSAT]</span></td></tr>
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{{STRUCTURE_2zpx| PDB=2zpx | SCENE= }}
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</table>
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== Disease ==
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[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).
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zp/2zpx_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zpx ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Tumour necrosis factor (TNF) is an important cytokine that induces an inflammatory response predominantly through the TNF receptor-1 (TNFR1). A crucial strategy for the treatment of many autoimmune diseases, therefore, is to block the binding of TNF to TNFR1. We previously identified a TNFR1-selective antagonistic mutant TNF (R1antTNF) from a phage library containing six randomized amino acid residues at the receptor-binding site (amino acids 84-89). Two R1antTNFs, R1antTNF-T2 (A84S, V85T, S86T, Y87H, Q88N and T89Q) and R1antTNF-T8 (A84T, V85P, S86A, Y87I, Q88N and T89R), were successfully isolated from this library. Here, we analysed R1antTNF-T8 using surface plasmon resonance spectroscopy and X-ray crystallography to determine the mechanism underlying the antagonistic activity of R1antTNF. The kinetic association/dissociation parameters of R1antTNF-T8 were higher than those of wild-type TNF, indicating more rapid bond dissociation. X-ray crystallographic analysis suggested that the binding mode of the T89R mutation changed from a hydrophobic to an electrostatic interaction, which may be responsible for the antagonistic behaviour of R1antTNF. Knowledge of these structure-function relationships will facilitate the design of novel TNF inhibitors based on the cytokine structure.
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===TNF Receptor Subtype One-selective TNF Mutant with Antagonistic Activity; R1antTNF-T8===
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Fast binding kinetics and conserved 3D structure underlie the antagonistic activity of mutant TNF: useful information for designing artificial proteo-antagonists.,Mukai Y, Nakamura T, Yoshioka Y, Shibata H, Abe Y, Nomura T, Taniai M, Ohta T, Nakagawa S, Tsunoda S, Kamada H, Yamagata Y, Tsutsumi Y J Biochem. 2009 Aug;146(2):167-72. Epub 2009 Apr 22. PMID:19386778<ref>PMID:19386778</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2zpx" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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2ZPX is a 3 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZPX OCA].
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*[[Tumor necrosis factor|Tumor necrosis factor]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Mukai, Y.]]
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[[Category: Large Structures]]
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[[Category: Nakamura, T.]]
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[[Category: Mukai Y]]
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[[Category: Tsutsumi, Y.]]
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[[Category: Nakamura T]]
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[[Category: Yamagata, Y.]]
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[[Category: Tsutsumi Y]]
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[[Category: Antagonistic activity]]
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[[Category: Yamagata Y]]
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[[Category: Cell membrane]]
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[[Category: Cytokine]]
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[[Category: Lipoprotein]]
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[[Category: Membrane]]
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[[Category: Myristate]]
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[[Category: Phage display system]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Secreted]]
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[[Category: Signal-anchor]]
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[[Category: Tnfr1 specific]]
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[[Category: Transmembrane]]
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[[Category: Trimer]]
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[[Category: Tumor necrosis factor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 25 12:21:45 2009''
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Current revision

TNF Receptor Subtype One-selective TNF Mutant with Antagonistic Activity; R1antTNF-T8

PDB ID 2zpx

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