The second Kunitz domain of human tissue factor pathway inhibitor: cloning, structure determination and interaction with factor Xa 1 1Edited by T. Richmond

Burgering, Maurits; Orbons, Leonard P. M.; Doelen, A. Van Der; Mulders, John W. M.; Theunissen, Henri J.M.; Grootenhuis, Peter D. J.; Bode, Wolfram; Huber, Robert; Stubbs, Milton T.

doi:10.1006/jmbi.1997.1029

Cited by 73 publications

(70 citation statements)

References 63 publications

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“…We follow the convention to sequentially numbering the mature protein without the signal peptide. High resolution structural studies have been carried out on K2 and K3 domains (6,7), but not on the K1 domain. K1 has been reported to bind and inhibit FVIIa and K2 binds and inhibits FXa (4).…”

Section: Tissue Factor Pathway Inhibitor (Tfpi)mentioning

confidence: 99%

Small Peptides Blocking Inhibition of Factor Xa and Tissue Factor-Factor VIIa by Tissue Factor Pathway Inhibitor (TFPI)

Dockal

Hartmann

Fries

et al. 2014

Journal of Biological Chemistry

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Background: Tissue factor pathway inhibitor (TFPI) inhibits coagulation factors Xa and VIIa. Results: A de novo synthesized 20-mer peptide that binds to TFPI was structurally and functionally characterized. Conclusion:The peptide binds to the Kunitz domain 1 of TFPI and blocks inhibition of factor Xa and factor VIIa by TFPI. Significance: The peptide can potentially prevent bleeding in hemophilia patients.

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Section: Tissue Factor Pathway Inhibitor (Tfpi)mentioning

confidence: 99%

Small Peptides Blocking Inhibition of Factor Xa and Tissue Factor-Factor VIIa by Tissue Factor Pathway Inhibitor (TFPI)

Dockal

Hartmann

Fries

et al. 2014

Journal of Biological Chemistry

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“…plasma concentration limits its impact. Molecular modeling suggests that electrostatic fields drive, in part, the interaction of FXa with TFPI (8,9). Basic groups of TFPI would secure contacts within the acidic loop 34 -40 of FXa, whereas an acidic patch may complement the basic autolysis loop of FXa (Arg 143 , His 145 , Lys 148 , and Arg 150 ), even though mutagenesis has failed to confirm its role (53).…”

Section: Figmentioning

confidence: 99%

“…In fact, a number of studies have established that exosite(s) must be critical in several FXa functions. Electrostatic interactions involving loop 34 -40 of FXa appear to play a significant role in binding to the second Kunitz domain of TFPI (8,9). FXa also appears to interact with a complementary surface on pentasaccharide-activated antithrombin (10), and the region of FXa topologically equivalent to exosite-2 of thrombin seems to be involved in the binding of heparin and FVa (11).…”

mentioning

confidence: 97%

The Elusive Role of the Potential Factor X Cation-binding Exosite-1 in Substrate and Inhibitor Interactions

Bianchini

Pike

Bonniec

2004

Journal of Biological Chemistry

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Coagulation factor X (FX) 1 is a vitamin K-dependent zymogen activated into FXa by cleavage at a single bond (Arg 15 -Ile 16 in the chymotrypsin numbering system 2 ) hydrolyzed by either of two complexes: FVIIa bound to tissue factor (TF), which triggers coagulation after injury, or FIXa associated with FVIIIa, which amplifies thrombin production after initiation of coagulation. FXa is the only endogenous prothrombin activator, but substantial thrombin production occurs only within the prothrombinase complex, where FXa binds to FVa in the presence of calcium on an appropriate phospholipid surface. Two inhibitors control FXa activity, viz. the tissue factor pathway inhibitor (TFPI) and antithrombin.Extended binding sites (exosites) play a crucial role in virtually any substrate, cofactor, or inhibitor recognition within the coagulation cascade. Perhaps best characterized is the case of thrombin taking advantage of two exosites for extended interactions in numerous functions (1). Exosite-1 is formed by a set of basic residues comprising loops 34 -40 and 70 -80, which neighbor each other in the folded structure (2); it interacts with fibrinogen, thrombomodulin, platelet activator receptor-1, FV, FVa, heparin cofactor II, and hirudin. Exosite-2, comprising loop 91-102 and helices 165-173 and 233-245 (3), is also formed by a set of basic residues that interact with heparin, with the chondroitin sulfate of thrombomodulin, and within prothrombin with kringle-2 (4). In FVII, the region corresponding to exosite-1 of thrombin is critical for FX activation (5, 6); in FIXa, this region is also important for FX activation in the absence of FVIII and for its inhibition by antithrombin in the absence of heparin (7). In contrast to thrombin, FVIIa, FIXa, and FXa share a negatively charged patch within segment 70 -80, whereas FXa is unique in that both loops 34 -40 and 70 -80 are negatively charged. Thus, the region of FXa corresponding to exosite-1 of thrombin forms a negative cluster, raising the question as to whether it could constitute a functional exosite. FXa has a unique macromolecule substrate, but exosites may also participate in its inhibition and/or in the activation of its zymogen. In fact, a number of studies have established that exosite(s) must be critical in several FXa functions. Electrostatic interactions involving loop 34 -40 of FXa appear to play a significant role in binding to the second Kunitz domain of TFPI (8,9). FXa also appears to interact with a complementary surface on pentasaccharide-activated antithrombin (10), and the region of FXa topologically equivalent to exosite-2 of thrombin seems to be involved in the binding of heparin and FVa (11). Above all, prothrombin recognition by prothrombinase undoubtedly involves one or more exosites on .In a previous study (15), we reported that the catalytic groove of FXa is minimally selective with unconstrained peptides and that FVa has little effect, if any, on this selectivity. These two observations therefore also favor the hypothesis that FXa uses seconda...

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“…Moreover, a trypsin inhibitor occuring in a complex containing a phospholipase A2 (PLA2) and a protease has also been reported [22]. The characteristically folded domain like that of a BPTI-like peptides is also found in several proteins, for example a human Alzheimer amyloid precursor protein [17], type VI collagen alpha3(VI) [27,41], tissue factor pathway inhibitor [1] and …”

Section: Introductionmentioning

confidence: 99%

Purification, characterization and molecular cloning of chymotrypsin inhibitor peptides from the venom of Burmese Daboia russelii siamensis

Guo

McClean²,

Shaw

et al. 2013

Peptides

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The second Kunitz domain of human tissue factor pathway inhibitor: cloning, structure determination and interaction with factor Xa 1 1Edited by T. Richmond

Cited by 73 publications

References 63 publications

Small Peptides Blocking Inhibition of Factor Xa and Tissue Factor-Factor VIIa by Tissue Factor Pathway Inhibitor (TFPI)

Small Peptides Blocking Inhibition of Factor Xa and Tissue Factor-Factor VIIa by Tissue Factor Pathway Inhibitor (TFPI)

The Elusive Role of the Potential Factor X Cation-binding Exosite-1 in Substrate and Inhibitor Interactions

Purification, characterization and molecular cloning of chymotrypsin inhibitor peptides from the venom of Burmese Daboia russelii siamensis

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