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4dtg

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Revision as of 23:30, 5 August 2016

Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model

Structural highlights

4dtg is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1tfx, 1adz
Gene:	LACI, TFPI, TFPI (AMINO ACIDS 119-178), TFPI1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

Publication Abstract from PubMed

Hemophilia is treated by intravenous replacement therapy with factor VIII (FVIII) or factor IX (FIX), either on demand to resolve bleeding, or as prophylaxis. Improved treatment may be provided by drugs designed for subcutaneous and less frequent administration with a reduced risk of inhibitor formation. Tissue factor pathway inhibitor (TFPI) down regulates the initiation of coagulation by inhibition of FVIIa/TF/FXa. Blockage of TFPI inhibition may facilitate thrombin generation in a hemophilic setting. A high-affinity (K(D) = 25 pM) monoclonal antibody, mAb 2021, against TFPI was investigated. Binding of mAb 2021 to TFPI effectively prevented inhibition of FVIIa/TF/FXa and improved clot formation in hemophilia blood and plasma. The binding epitope on Kunitz-type protease inhibitor domain 2 of TFPI was mapped by crystallography, and showed an extensive overlap with the FXa contact region highlighting a structural basis for its mechanism of action. In a rabbit hemophilia model, intravenous or subcutaneous dose significantly reduced cuticle bleeding. mAb 2021 showed effect comparable to that of rFVIIa. Cuticle bleeding in the model was reduced for at least 7 days by a single intravenous dose of mAb 2021. This study suggests that neutralization of TFPI by mAb 2021 may constitute a novel treatment option in hemophilia.

Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model.,Hilden I, Lauritzen B, Sorensen BB, Clausen JT, Jespersgaard C, Krogh BO, Bowler AN, Breinholt J, Gruhler A, Svensson LA, Petersen HH, Petersen LC, Balling KW, Hansen L, Hermit MB, Egebjerg T, Friederichsen B, Ezban M, Bjorn SE Blood. 2012 May 4. PMID:22563084^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hilden I, Lauritzen B, Sorensen BB, Clausen JT, Jespersgaard C, Krogh BO, Bowler AN, Breinholt J, Gruhler A, Svensson LA, Petersen HH, Petersen LC, Balling KW, Hansen L, Hermit MB, Egebjerg T, Friederichsen B, Ezban M, Bjorn SE. Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model. Blood. 2012 May 4. PMID:22563084 doi:10.1182/blood-2012-01-401620

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4dtg"

@@ Line 1: / Line 1: @@
 ==Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model==
 <StructureSection load='4dtg' size='340' side='right' caption='[[4dtg]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4dtg]] is a 3 chain structure with sequence 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=4DTG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DTG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4dtg]] 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=4DTG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DTG FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tfx|1tfx]], [[1adz|1adz]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LACI, TFPI, TFPI (AMINO ACIDS 119-178), TFPI1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LACI, TFPI, TFPI (AMINO ACIDS 119-178), TFPI1 ([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=4dtg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dtg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dtg RCSB], [http://www.ebi.ac.uk/pdbsum/4dtg 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=4dtg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dtg OCA], [http://pdbe.org/4dtg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dtg RCSB], [http://www.ebi.ac.uk/pdbsum/4dtg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dtg ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4dtg" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Antibody|Antibody]]
+*[[Tissue factor pathway inhibitor|Tissue factor pathway inhibitor]]
-*[[Monoclonal Antibody|Monoclonal Antibody]]
+*[[3D structures of antibody|3D structures of antibody]]
+*[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Breinholt, J]]
 [[Category: Hilden, I]]

4dtg

From Proteopedia

Revision as of 23:30, 5 August 2016

Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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