ライフサイエンスコーパス: factor XIa

1 11.2 +/- 3.2 nM vs K(d) 8.63 +/- 1.06 nM for factor XIa).

2 n(-1) with factor XIIa and 2 nm.min(-1) with factor XIa.

3 ctor XIIa, and 1.3-14 (mean = 8) min(-1) for factor XIa.

4 nvolves the actions of factor Xa with PZ and factor XIa.

5 nt, reversible, and competitive inhibitor of factor XIa.

6 ctivation by Factor VIIa-tissue factor or by Factor XIa.

7 r IX is present on the third apple domain of factor XIa.

8 s present on the noncatalytic heavy chain of factor XIa.

9 hion, but also directly inhibits coagulation factor XIa.

10 inding site is located in the light chain of factor XIa.

11 ytic domain near the heparin binding site of factor XIa.

12 in recognition of factor IX by the protease factor XIa.

13 ge of a tripeptidic chromogenic substrate by factor XIa.

14 udy the mechanism of factor IX activation by factor XIa.

15 ely 10-fold lower than their affinity toward factor XIa.

16 -Ile(370) bonds by thrombin, factor XIIa, or factor XIa.

17 caused by a specific defect in activation by factor XIa.

18 tivated to factor IXabeta by factor VIIa and factor XIa.

19 Factor VIIa (10 nM) and factor XIa (1 nM) are not observed to activate factor VI

20 f kallikrein-C1 inhibitor complexes, without Factor XIa activation and coagulation (see the related a

21 Consistent with this premise, inhibition of factor XIa activation of factor IX by aprotinin (Ki 0.89

22 It has been postulated that the two factor XIa active sites cleave both factor IX peptide bo

23 ight kininogen may play a role in regulating factor XIa activity.

24 Factor XIa also cleaves factor IX preferentially after A

25 -binding site within the catalytic domain of factor XIa also displaced [125I]factor XIa from the surf

26 ep, M(r) approximately 12000) inhibited both factor XIa amidolytic activity and factor IX activation

27 Factor XIa and 1/2-FXIa activate the substrate factor IX

28 The rate constants for factor XIa and catalytic domain inhibition by recombinan

29 et al have established, in human blood, that factor XIa and polyphosphate make significant contributi

30 iciently long to provide a template to which factor XIa and protease nexin-2 molecules can bind simul

31 vation by alpha-thrombin, beta-thrombin, and factor XIa and that these reactions are supported by pol

32 II are localized to the catalytic domain of factor XIa and the Kunitz domain of protease nexin II.

33 tes ZPI to inhibit free factor Xa as well as factor XIa and therefore may play a physiologically and

34 y domain, and it inhibits plasma kallikrein, factor XIa, and plasmin.

35 that factor IX binds to free and S2366-bound factor XIa at exosites.

36 ytic domain loop were used as competitors in factor XIa binding and inhibition studies.

37 on activated platelets, suggesting that the factor XIa binding site for platelets is not located in

38 ese results provide compelling evidence that factor XIa binding to the polyanions, dextran sulfate an

39 The data demonstrate that factor XIa binds with comparable affinity to factors IX

40 ivated normally by its physiologic activator factor XIa, but its phospholipid-dependent activation by

41 Inhibition of factor XIa by protease nexin II (K(i) approximately 450

42 association rate constants for inhibition of factor XIa by protease nexin II [(3.35 +/- 0.35) x 10(6)

43 xamined binding of factors IX and IXabeta to factor XIa by surface plasmon resonance.

44 ne proteases, including cationic trypsin and factor XIa, by 2 orders of magnitude.

45 In contrast, activation by factor XIa.Ca2+ led to proteolysis at Arg318-Ser319[150-

46 The factor XIa catalytic domain contains a cysteine-constrai

47 Synthesized peptides representative of the factor XIa catalytic domain loop were used as competitor

48 S2366 cleavage by isolated factor XIa catalytic domain was competitively inhibited

49 X alpha accumulated during activation by the factor XIa catalytic domain, demonstrating the importanc

50 a high-affinity heparin-binding site in the factor XIa catalytic domain.

51 We conclude that factor XIa-catalyzed activation of factor IX proceeds vi

52 n be explained by one of two mechanisms: (1) factor XIa-catalyzed activation proceeds via a singly-cl

53 In contrast, inhibition of factor XIa cleavage of S2366 by factor IX (Ki 224 +/- 32

54 Factor XIa cleavage of the tripeptide substrate S2366 wa

55 We compared the factor XIa cleavage rates of free factor IX alpha and fa

56 ), prothrombinase (factor Va/factor Xa), and factor XIa complexes on PS-exposed activated platelets.

57 XIa (Ki approximately 1.4 nM) and a chimeric factor XIa containing the Apple 3 domain of prekallikrei

58 hibition of the isolated catalytic domain of factor XIa demonstrates a similar potentiation by hepari

59 Factor XIa devoid of the A3 domain displayed a major def

60 during coagulation, and that each half of a factor XIa dimer behaves as an independent enzyme with r

61 in analyses, suggest that the active site of factor XIa does not contribute significantly to the affi

62 mogen) platelet binding site and exposes the factor XIa (enzyme) platelet binding site within the cat

63 primary constituents of the contact pathway: factor XIa, factor XIIa, and plasma kallikrein, in the p

64 e affinity of leupeptin and aprotinin to the factor XIa-factor IX complex only approximately 10-fold

65 Ki approximately 2.7 nM) competed with [125I]factor XIa for binding sites on activated platelets, sug

66 , (538)H, and (539)K binds and competes with factor XIa for heparin-binding in a manner nearly identi

67 ic domain of factor XIa also displaced [125I]factor XIa from the surface of activated platelets (Ki a

68 n the intrinsic pathway of blood coagulation factor XIa (FXIa) activates factor IX (FIX) by cleaving

69 During blood coagulation, the protease factor XIa (fXIa) activates factor IX (fIX).

70 Heparin accelerates inhibition of factor XIa (fXIa) by the serpins antithrombin (AT) and C

71 Factor XIa (FXIa) cleaved chem163S, generating a novel c

72 Factor XIIa (FXIIa) and factor XIa (FXIa) contribute to thrombosis in animal mod

73 e autolysis loop of the coagulation protease factor XIa (fXIa) for inhibition by serpins.

74 Antithrombotic agents that are inhibitors of factor XIa (FXIa) have the potential to demonstrate robu

75 Factor XIa (FXIa) is a blood coagulation enzyme that is

76 Inhibition of factor XIa (FXIa) is a novel paradigm for developing ant

77 Factor XIa (FXIa) is a serine protease important for ini

78 Factor XIa (fXIa) is being recognized as a prime target

79 IX (FIX) to an exosite on the heavy chain of factor XIa (FXIa) is essential for the optimal activatio

80 To select residues in coagulation factor XIa (FXIa) potentially important for substrate an

81 Human coagulation factor XIa (FXIa), a serine protease activated by site-s

82 Moreover, the activity of factor XIa (FXIa), but not FXIIa, was higher in APP-KO m

83 related proteases (such as Factor Xa (FXa), Factor XIa (FXIa), urokinase-type plasminogen activator

84 lycan-binding proteins (GBPs), such as human factor XIa (FXIa), we screened a library of 26 synthetic

85 posits, is a potent inhibitor of coagulation factor XIa (FXIa).

86 a potent inhibitor of the blood coagulation Factor XIa (FXIa).

87 d competitive inhibitor of blood coagulation factor XIa (FXIa).

88 e replaced it with Ala or Val in coagulation factor XIa (FXIa).

89 anoside (SPGG) as an allosteric inhibitor of factor XIa (FXIa).

90 ctivators, plasma kallikrein and coagulation factor XIa (FXIa).

91 It seems likely that factor XIa-generated intermediates observed under some r

92 The termination of factor XIa generation by added hirudin in the factor XI

93 -2366) and on the activation of factor IX by factor XIa have been investigated.

94 vation suggests that binding of factor IX to factor XIa heavy chain affects the interactions of leupe

95 factor IX binds initially to exosites on the factor XIa heavy chain, followed by interaction at the a

96 domain, demonstrating the importance of the factor XIa heavy chain.

97 sion of a potent inhibitor of Factor IXa and Factor XIa (ie, protease nexin-2/ amyloid beta-protein p

98 d <1% of the coagulant activity of wild type factor XIa in a plasma coagulation assay, whereas the ch

99 tein Z-dependent protease inhibitor inhibits factor XIa in a protein Z-independent fashion.

100 with a K(d) = 86 +/- 15 nM and competes with factor XIa in binding to heparin, K(i) = 241 +/- 37 nM.

101 llikrein, activated forms of factor XII, and factor XIa in plasma.

102 Besides factor Xa, ZPI also inhibits factor XIa in the absence of PZ, phospholipids, and Ca(+

103 e demonstrated roles for the factor XIIa and factor XIa in thrombosis.

104 est that the major interactions required for factor XIa inhibition by protease nexin II are localized

105 ions with 32-64 saccharide units potentiated factor XIa inhibition by protease nexin-2 in a size- and

106 No effect on factor XIa inhibition by protease nexin-2 was observed w

107 Heparin-mediated enhancement of factor XIa inhibition by protease nexin-2 was partially

108 phenotype than PZ deficiency, implying that factor XIa inhibition by ZPI is physiologically relevant

109 and the extent (99% vs 93% at 30 minutes) of factor XIa inhibition by ZPI.

110 The zymogen, factor XI, and the enzyme, factor XIa, interact specifically with functional recept

111 Factor XIa is a serine protease which participates in bo

112 Factor XIa is inhibited by a recombinant Kunitz domain w

113 The isolated catalytic domain of factor XIa is inhibited by protease nexin II with an inh

114 In contrast, activation by factor XIa is not phospholipid-dependent, raising questi

115 Factor IX activation by factor XIa is thought to proceed through the singly-clea

116 Addition of factor XIa, IXa, VIIIa, or Va failed to correct the PTT

117 oop or a C-terminal heparin-binding region), factors XIa, IXa, Xa, and thrombin; group B (binding by

118 to factor XIa (K(i) 34 nm) and activation by factor XIa (K(i) 33 nm).

119 s a potent inhibitor of factor IX binding to factor XIa (K(i) 34 nm) and activation by factor XIa (K(

120 metry of 1.9 +/- 0.4 mol of factor IX/mol of factor XIa (Kd = 70 +/- 40 nm).

121 an plasma kallikrein (Ki = 0.3 nM) and human factor XIa (Ki = 6 nM).

122 Both factor XIa (Ki approximately 1.4 nM) and a chimeric fact

123 ithout free intermediate generation, whereby factor XIa makes both proteolytic cleavages in a single

124 A chimeric factor XIa molecule with the A3 domain replaced with A3

125 one inhibited active site, or a recombinant factor XIa monomer.

126 astin time (aPTT) assay and was activated by factor XIa more slowly than wild-type factor IX (FIXwt).

127 alenesulfonyl)glutamylglycylarginyl- (DEGR-) factor XIa observed when the fluorophore was in complex

128 gher than the Km for activation by wild type factor XIa or the other factor XI/PK chimeras (0.11-0.37

129 During hemostasis, factor IX is activated by factors XIa or VIIa, by cleavage of the peptide bonds af

130 ces for factor XI activation by factor XIIa, factor XIa, or thrombin.

131 Activated factor XI (factor XIa) participates in blood coagulation by activat

132 The Km for activation of factor IX by factor XIa/PKA3 (12.7 microM) is more than 30-fold highe

133 factor pathway inhibitor-2 (TFPI-2) inhibits factor XIa, plasma kallikrein, and factor VIIa/tissue fa

134 ed with KD1-WT, the KD1-L17R did not inhibit factor XIa, plasma kallikrein, or factor VIIa/tissue fac

135 These data suggest that factor XIa plays a significant role in venous thrombosis

136 This is due primarily to murine factor XIa preferentially cleaving a site on zymogen fac

137 vation in plasma, conversion of factor XI to factor XIa proceeds through an intermediate with one act

138 by providing a template for the assembly of factor XIa-protease nexin-2 complexes, and only heparin

139 vage of factor IX by four single active site factor XIa proteases.

140 nvolved in factor IX activation, recombinant factor XIa proteins containing alanine substitutions for

141 Activated coagulation factor XI (factor XIa) proteolytically cleaves its substrate, facto

142 luorescence titration of active site-labeled factor XIa revealed a binding stoichiometry of 1.9 +/- 0

143 d to identify the molecular subdomain within factor XIa that binds to activated platelets.

144 ition accompanies conversion of factor XI to factor XIa that conceals the Apple 3 domain factor XI (z

145 effect, suggesting that the binding site in factor XIa that interacts with the platelet surface resi

146 le370-Val607) inhibited the binding of [125I]factor XIa to the platelets (Ki approximately 3.5 nM), w

147 erations of ZPI reactions with factor Xa and factor XIa to yield second order rate constants approach

148 contribute significantly to the affinity of factor XIa toward factor IX.

149 e development during factor IX activation by factor XIa when using a low substrate to enzyme ratio (4

150 potent inhibitors of factor IX activation by factor XIa, whereas antibodies against the A2 (1A6) and

151 Recombinant factor IX bound to factor XIa with a K(d) of 107 nm, whereas factor IX with

152 s the ability of protease nexin-2 to inhibit factor XIa with a parabolic concentration dependence, pr

153 Kunitz-type domain, is a potent inhibitor of factor XIa with an inhibition constant of 250-400 pM.

154 Plasma factors IX and IXabeta bind to factor XIa with K(d) values of 120 +/- 11 nm and 110 +/-

155 ediate formation was detected with 1/2-FXIa, factor XIa with one inhibited active site, or a recombin

156 is the zymogen of a dimeric plasma protease, factor XIa, with two active sites.

157 ts inhibitory interaction with factor Xa and factor XIa, ZPI is proteolytically cleaved with the rele