View source for 5nmv


==Crystal structure of 2F22 Fab fragment against TFPI1==
<StructureSection load='5nmv' size='340' side='right'caption='[[5nmv]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nmv]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus Mus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NMV 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]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5nmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nmv OCA], [https://pdbe.org/5nmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nmv RCSB], [https://www.ebi.ac.uk/pdbsum/5nmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nmv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TFPI1_HUMAN TFPI1_HUMAN] Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action and also the ability to associate with lipoproteins in plasma.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: Initiation of coagulation is induced by binding of activated factor VII (FVIIa) to tissue factor (TF) and activation of factor X (FX) in a process regulated by tissue factor pathway inhibitor (TFPI). TFPI contains three Kunitz-type protease inhibitor domains (K1-K3) of which K1 and K2 block the active sites of FVIIa and FXa respectively. OBJECTIVE: To produce a monoclonal antibody (mAb) directed towards K1, to characterize the binding epitope, and to study its effect on TFPI inhibition. METHODS: A monoclonal antibody, mAb2F22, was raised against the N-terminal TFPI(1-79) fragment. Binding data were obtained by surface plasmon resonance analysis. The Fab-fragment of mAb2F22, Fab2F22, was expressed and the structure of its complex with TFPI(1-79) determined by X-ray crystallography. Effects of mAb2F22 on TFPI inhibition were measured in buffer- and plasma- based systems. RESULTS: mAb2F22 bound exclusively to K1 of TFPI (KD ~1 nM) and not to K2. The crystal structure of Fab2F22/TFPI (1-79) mapped an epitope on K1 including seven residues upstream of the domain. TFPI inhibition of TF/FVIIa amidolytic activity was neutralized by mAb2F22, although the binding epitope on K1 did not include the P1 residue. Binding of mAb2F22 to K1 blocked TFPI inhibition of the FXa amidolytic activity and normalised haemostasis in haemophilia human A-like plasma and whole blood. CONCLUSION: mAb2F22 blocked TFPI inhibition of both FVIIa and FXa activities and mapped a FXa exosite for binding to K1. It reversed TFPI feed-back inhibition of TF/FVIIa-induced coagulation and restored clot formation in FVIII-neutralized human plasma and blood. This article is protected by copyright. All rights reserved.

Factor Xa and VIIa inhibition by Tissue Factor Pathway Inhibitor is prevented by a monoclonal antibody to its Kunitz-1 domain.,Augustsson C, Svensson A, Kjaer B, Chao TY, Wenjuan X, Krogh BO, Breinholt J, Clausen JT, Hilden I, Petersen HH, Petersen LC J Thromb Haemost. 2018 Mar 12. doi: 10.1111/jth.14000. PMID:29532595<ref>PMID:29532595</ref>

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

==See Also==
*[[Tissue factor pathway inhibitor|Tissue factor pathway inhibitor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus]]
[[Category: Petersen HH]]
[[Category: Svensson LA]]