View source for 1tfh


==EXTRACELLULAR DOMAIN OF HUMAN TISSUE FACTOR==
<StructureSection load='1tfh' size='340' side='right'caption='[[1tfh]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1tfh]] is a 2 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=1TFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TFH 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]] 2.4&#8491;</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=1tfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tfh OCA], [https://pdbe.org/1tfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tfh RCSB], [https://www.ebi.ac.uk/pdbsum/1tfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tfh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TF_HUMAN TF_HUMAN] Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.<ref>PMID:12652293</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tf/1tfh_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1tfh ConSurf].
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== Publication Abstract from PubMed ==
The tissue factor (TF)-initiated blood coagulation protease cascade can be greatly inhibited in vivo by a potent anti-human-TF monoclonal antibody, 5G9. This antibody binds the carboxyl module of the extracellular domain of TF with a nanomolar binding constant and inhibits the formation of the TF.VIIa.X ternary initiation complex. We have determined the crystal structures of the extra-cellular modules of human TF, Fab 5G9, and their complex (TF.5G9) to 2.4 A, 2. 5 A, and 3.0 A, respectively, and measured the apparent inhibition constants of 5G9 on a panel of TF mutants. In our unliganded TF structure, a 7 degrees change in the relative orientation between the D1 and D2 modules was observed when compared with other published TF structures. Comparison of the free and bound Fab 5G9 indicates that small segmental and side chain variation of the antibody complementarity determining regions occurred on complexation with TF. The antibody-antigen recognition involves 18 TF antigen residues and 19 Fab residues from six CDR with one of the largest buried surface areas seen to date. A combination of structural and mutagenesis data indicate that Tyr156, Lys169, Arg200, and Lys201 play the major role in the antibody recognition. The TF. 5G9 structure provides insights into the mechanism by which the antibody 5G9 inhibits formation of the TF.VIIa.X ternary complex.

The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF.G9 complex.,Huang M, Syed R, Stura EA, Stone MJ, Stefanko RS, Ruf W, Edgington TS, Wilson IA J Mol Biol. 1998 Feb 6;275(5):873-94. PMID:9480775<ref>PMID:9480775</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1tfh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tissue factor|Tissue factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Edgington TS]]
[[Category: Huang M]]
[[Category: Ruf W]]
[[Category: Stefanko RS]]
[[Category: Stone MJ]]
[[Category: Stura EA]]
[[Category: Syed R]]
[[Category: Wilson IA]]