Tissue factor pathway inhibitor: Difference between revisions
Michal Harel (talk | contribs) New page: <StructureSection load='1tfx' size='340' side='right' caption='Human tissue factor pathway inhibitor I kunitz domai II complex with trypsin (PDB code 1tfx) comp' scene=''> '''Tissue f... |
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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'> | |||
<StructureSection load=' | |||
== 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. | |||
== Relevance == | == Relevance == | ||
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/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/> | ||
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