Tissue factor pathway inhibitor

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<StructureSection load='1tfx' size='340' side='right' caption='Human tissue factor pathway inhibitor I kunitz domai II (grey and green) complex with trypsin (pink and yellow) and Ca+2 ion (PDB code [[1tfx]]) comp' scene=''>
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<StructureSection load='' size='350' side='right' caption='Human tissue factor pathway inhibitor 2 Kunitz domain I (green) complex with trypsin (cyan) and Ca+2 ion (PDB code [[1zr0]])' scene='70/707370/Cv/1'>
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'''Tissue factor pathway inhibitor''' (TFPI) is a protease inhibitor which inhibits coagulation factor Xa and VIIa. TFPI contains three Kunitz domains. The Kunitz domain is disulfide-rich and is arranged to form a twisted two-stranded antiparallel β sheet followed by an α helix. Kunitz I domain inhibits VIIa coagulation factor while Kunitz II domain inhibits Xa.
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== Function ==
== Function ==
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'''Tissue factor pathway inhibitor''' (TFPI) is a protease inhibitor which inhibits coagulation factor Xa and VIIa<ref>PMID:9112630</ref>. TFPI contains three Kunitz domains. The Kunitz domain is disulfide-rich and is arranged to form a twisted two-stranded antiparallel β sheet followed by an α helix. Kunitz I and II domains inhibit VIIa coagulation factor while Kunitz II domain inhibits Xa. Kunitz III domains probably involved in the interactions with lipoproteins.
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== Disease ==
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== Relevance ==
== Relevance ==
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The expression of hTFPI-2 in tumors is inversely related to their malignancy<ref>PMID:18000791</ref>. TFPI inhibitors are investigated as therapeutic agents agains hemophilia<ref>PMID:27207418</ref>.
== Structural highlights ==
== Structural highlights ==
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In the complex of TFPI-2 and trypsin, <scene name='70/707370/Cv/6'>hydrophobic residues of TFPI-2 interact with hydrophobic patch</scene> of trypsin. An <scene name='70/707370/Cv/7'>Arg residue which is the P1 residue of TFPI-2 interacts with Asp - the S1 residue</scene> of trypsin<ref>PMID:15932872</ref>. <scene name='70/707370/Cv/8'>Ca coordination site</scene>. Water molecules are shown as red spheres.
</StructureSection>
</StructureSection>
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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Tissue factor pathway inhibitor domains: kunitz I 29-118; kunitz II 121-178; kunitz III 210-270
[[1adz]] – hTFPI-1 kunitz domain II (mutant) – human - NMR<br />
[[1adz]] – hTFPI-1 kunitz domain II (mutant) – human - NMR<br />
[[1irh]] – hTFPI-1 kunitz domain III - NMR<br />
[[1irh]] – hTFPI-1 kunitz domain III - NMR<br />
[[1tfx]] – hTFPI-1 kunitz domain II + trypsin <br />
[[1tfx]] – hTFPI-1 kunitz domain II + trypsin <br />
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[[6bx8]] – hTFPI-1 kunitz domain I (mutant) + trypsin <br />
[[1zr0]] – hTFPI-2 kunitz domain I + trypsin <br />
[[1zr0]] – hTFPI-2 kunitz domain I + trypsin <br />
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[[5nmv]] – hTFPI-1 kunitz domain I + antibody <br />
[[4dtg]] – hTFPI-1 kunitz domain II + antibody <br />
[[4dtg]] – hTFPI-1 kunitz domain II + antibody <br />
[[4bqd]] – hTFPI-1 kunitz domain I + peptide <br />
[[4bqd]] – hTFPI-1 kunitz domain I + peptide <br />
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[[7v1n]] – hTFPI-1 + toxin B <br />
== References ==
== References ==
<references/>
<references/>
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[[Category:Topic Page]]

Current revision

Human tissue factor pathway inhibitor 2 Kunitz domain I (green) complex with trypsin (cyan) and Ca+2 ion (PDB code 1zr0)

Drag the structure with the mouse to rotate

3D Structures of tissue factor pathway inhibitor

Updated on 25-April-2022

Tissue factor pathway inhibitor domains: kunitz I 29-118; kunitz II 121-178; kunitz III 210-270

1adz – hTFPI-1 kunitz domain II (mutant) – human - NMR
1irh – hTFPI-1 kunitz domain III - NMR
1tfx – hTFPI-1 kunitz domain II + trypsin
6bx8 – hTFPI-1 kunitz domain I (mutant) + trypsin
1zr0 – hTFPI-2 kunitz domain I + trypsin
5nmv – hTFPI-1 kunitz domain I + antibody
4dtg – hTFPI-1 kunitz domain II + antibody
4bqd – hTFPI-1 kunitz domain I + peptide
7v1n – hTFPI-1 + toxin B

References

  1. ↑ Kato H. Tissue factor pathway inhibitor; its structure, function and clinical significance. Pol J Pharmacol. 1996 Jan-Feb;48(1):67-72. PMID:9112630
  2. ↑ Sierko E, Wojtukiewicz MZ, Kisiel W. The role of tissue factor pathway inhibitor-2 in cancer biology. Semin Thromb Hemost. 2007 Oct;33(7):653-9. PMID:18000791 doi:http://dx.doi.org/10.1055/s-2007-991532
  3. ↑ Peterson JA, Maroney SA, Mast AE. Targeting TFPI for hemophilia treatment. Thromb Res. 2016 May;141 Suppl 2:S28-30. doi: 10.1016/S0049-3848(16)30359-0. PMID:27207418 doi:http://dx.doi.org/10.1016/S0049-3848(16)30359-0
  4. ↑ Schmidt AE, Chand HS, Cascio D, Kisiel W, Bajaj SP. Crystal structure of Kunitz domain 1 (KD1) of tissue factor pathway inhibitor-2 in complex with trypsin. Implications for KD1 specificity of inhibition. J Biol Chem. 2005 Jul 29;280(30):27832-8. Epub 2005 Jun 2. PMID:15932872 doi:10.1074/jbc.M504105200

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