Tissue factor pathway inhibitor: Difference between revisions
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<StructureSection load=' | <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'> | ||
== Function == | == Function == | ||
'''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. | '''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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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>. | 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 == | ||
In the complex of TFPI-2 and trypsin, <scene name='70/707370/Cv/ | 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}} | ||
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 /> | ||
[[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 /> | ||
[[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 /> | ||
[[7v1n]] – hTFPI-1 + toxin B <br /> | |||
== References == | == References == | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | |||
Latest revision as of 11:20, 25 April 2022
FunctionTissue 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. RelevanceThe expression of hTFPI-2 in tumors is inversely related to their malignancy[2]. TFPI inhibitors are investigated as therapeutic agents agains hemophilia[3]. Structural highlightsIn the complex of TFPI-2 and trypsin, of trypsin. An of trypsin[4]. . Water molecules are shown as red spheres. |
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3D Structures of tissue factor pathway inhibitor3D 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
ReferencesReferences
- ↑ Kato H. Tissue factor pathway inhibitor; its structure, function and clinical significance. Pol J Pharmacol. 1996 Jan-Feb;48(1):67-72. PMID:9112630
- ↑ 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
- ↑ 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
- ↑ 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