Tissue factor pathway inhibitor

From Proteopedia

Human tissue factor pathway inhibitor 2 Kunitz domain I (green) complex with trypsin (cyan) and Ca+2 ion (PDB code 1zr0) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Tissue factor pathway inhibitor (TFPI) is a protease inhibitor which inhibits coagulation factor Xa and VIIa[1]. 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. Relevance The expression of hTFPI-2 in tumors is inversely related to their malignancy[2]. TFPI inhibitors are investigated as therapeutic agents agains hemophilia[3]. Structural highlights In the complex of TFPI-2 and trypsin, of trypsin. An of trypsin[4]. . Water molecules are shown as red spheres.

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