ライフサイエンスコーパス: FXa

1 FXa also cleaves FVIII/FVIIIa at Arg(336) and Arg(562) r

2 FXa and the noncanonical PAR3 tethered-ligand peptide in

3 FXa generation assays and Western blotting, used to moni

4 FXa inhibition and PAR-2 deficiency in nonhematopoietic

5 FXa is the lone enzyme responsible for the production of

6 FXa signalling via activation of protease-activated rece

7 FXa(I16L) also reduces the anticoagulant-associated blee

8 FXa(I16L) may be able to fill an important unmet clinica

9 FXa(I16L) may provide an effective strategy to enhance b

10 des, FVa residues 493-506 were proposed as a FXa binding site.

11 Xa's active site serine was depolarized in a FXa concentration-dependent fashion in the presence of m

12 ion, ZPI-CD-helix(alpha1-PI) inhibition of a FXa mutant containing a mutation in the heparin-binding

13 ssociated factor V(a) (FVa) and factor X(a) (FXa) serve as the essential prothrombin-activating compl

14 ts such that structural data on PS-activated FXa is required to understand the structure of the FXa d

15 FXI (FXIa) is FIX, leading to FX activation (FXa) and thrombin generation.

16 Because of its inherent catalytic activity, FXa(I16L) is more potent (by >50-fold) in the hemostasis

17 nzamidine (35) with 0.83 nM activity against FXa and excellent selectivity over similar serine protea

18 rs, though with moderate selectivity against FXa.

19 bition of both FIXa in the FXase complex and FXa in the prothrombinase complex.

20 -specific fluorescent derivatives of FVa and FXa after laser injury in the mouse cremaster arteriole.

21 Although bound FVa and FXa may have been present on the platelet core at the ni

22 te high affinity association between FVa and FXa.

23 resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expre

24 physiological concentrations of TF:FVIIa and FXa.

25 ous "caps" with increased Annexin V, FX, and FXa binding were observed, indicating relevance of this

26 required for optimal inhibition of FXIa and FXa.

27 ed intracellular Ca(2+) release in HUVEC and FXa reactive IgG from patients with APS and/or SLE poten

28 In hemophilic plasma, FXa(I16L) and FXa(V17A) have prolonged half-lives compared with wild-t

29 Notably, assembly of FXa(I16L) and FXa(V17A) on activated platelets with factor Va to form

30 with zymogen-like properties (FXa(I16L) and FXa(V17A)) circumvent these limitations.

31 factor X through mutagenesis (FXa(I16L) and FXa(V17A)) not only alters active site function, but als

32 mpared to healthy control subjects' IgG, and FXa alone.

33 interfere with inactivation of thrombin and FXa by antithrombin (AT).

34 FIXa) is homologous to those of thrombin and FXa, we hypothesized that some aPLs in APS bind to FIXa

35 o FXa and that the levels of plasma IgG anti-FXa Ab in 38 APS patients were significantly higher than

36 pid Ab with FXa and the presence of IgG anti-FXa Ab in APS patients and investigated the effects of F

37 f, 5 of 38 APS patients (13.2%) had IgG anti-FXa Ab.

38 ide displayed a significantly increased anti-FXa activity compared with those of the pentasaccharide,

39 Despite the lower anti-FXa activity, dose reduction preserved the efficacy of e

40 L [22.7] to 16.0 ng/mL [14.5]) and mean anti-FXa activity by 25% (from 0.85 IU/mL [0.76] to 0.64 IU/m

41 fully-retained in the affinity purified anti-FXa IgG sub-fraction.

42 Combined, these results indicate that anti-FXa Ab may contribute to thrombosis by interfering with

43 igatran and the prothrombin time or the anti-FXa for rivaroxaban.

44 ts with data available) and mean trough anti-FXa activity (0.35-0.85 IU/mL in 2865 patients).

45 APC, FXa, and the noncanonical PAR3 tethered-ligand peptide i

46 ected behavior of an increase in activity as FXa bound to membranes, but instead suggested the existe

47 in FXI- or FIX-deficient plasma, as well as FXa-initiated clotting times in FX-deficient plasma.

48 ed to have different specificity for binding FXa and FIXa while retaining compatibility as substrate

49 In a model system, compound 3 blocked FXa inhibition by TFPI (EC50 = 11 nM) and inhibition of

50 ot detectable for FX, catalytic site-blocked FXa, thrombin, and 12 other enzymes.

51 novel antithrombotic peptide exhibiting both FXa inhibition and anti-platelet aggregation activities,

52 und that, albeit with different timing, both FXa/PCPS and E coli infusion led to robust thrombin and

53 equence LTFPRIVFVLG was identified with both FXa inhibition and anti-platelet aggregation activities.

54 lded a surprisingly modest decrease in bound FXa and FVa with little impact on fibrin formation.

55 Zn(2+)-containing PS bound FXa more efficiently (K(d)(app)=9.3 nM) than Zn(2+)-defi

56 e activity and structure of human and bovine FXa.

57 n factor V (FV), which has been activated by FXa.

58 Tie2 activation by FXa required PAR3 and EPCR.

59 ting and inactivating cleavages catalyzed by FXa that is modulated in large part by sequences flankin

60 n of EPCR promoted PAR1 and PAR2 cleavage by FXa in the ternary complex but did not alter PAR2 cleava

61 each of the above antibodies was examined by FXa generation assays.

62 Factor (F)VIII can be activated to FVIIIa by FXa following cleavages at Arg(372), Arg(740), and Arg(1

63 and directly inhibits thrombin generated by FXa/FVa (prothrombinase complex).

64 ever, the activity of DeltaC2 as measured by FXa generation and one-stage clotting assays retained 76

65 olecule-1 in sickle mice was not mediated by FXa or thrombin.

66 ion-dependent induction of Ca(2+) release by FXa that was potentiated by APS-IgG and SLE/APS- IgG com

67 of activation of prothrombin to thrombin by FXa in the presence of 400 muM C6PS by 14 000- to 15 000

68 Using pure component FXa inhibition assays, we found that although FV alone d

69 e inhibitor to hinder antithrombin-dependent FXa inactivation, paradoxically allowing uninhibited FXa

70 ssue factor-factor VIIa (TF-FVIIa)-dependent FXa generation.

71 ity for A3-C1-C2 to inhibit FVIIIa-dependent FXa generation in the presence of phospholipid was poor

72 sed blood coagulation scheme in which direct FXa-mediated FV activation occurs in the initiation phas

73 sis than the dysregulation of the downstream FXa and thrombin.

74 ing reciprocal activation of FVII/TF by each FXa mutant were impaired.

75 /without ZPI/protein Z were diluted in EDTA; FXa activity was measured after reversal of its inhibiti

76 (2+) is required for PS-direct and efficient FXa binding and may play a role in stabilizing PS confor

77 Protein S enhances FXa inhibition by TFPIalpha.

78 f K3 (R199L, TFPI(K3P1)) produced equivalent FXa inhibition in the absence of PS, whereas the respons

79 n that is strongly implicated as an extended FXa binding surface in the prothrombinase complex.

80 , we show that a variant coagulation factor, FXa(I16L), rapidly restores hemostasis in the presence o

81 All of them, including factors IXa (FIXa), FXa/FX, FVa, FVIII, prothrombin, and PS-sensitive marker

82 ctivity of FIXa with AT, we prepared an FIXa/FXa chimera in which the 39-loop of the protease was rep

83 (increasing FXa concentration) and at fixed FXa concentration (increasing membrane concentration).

84 lar FXIa inhibitory activity with >1000-fold FXa selectivity and >100-fold thrombin selectivity.

85 cal vein endothelial cells (HUVEC) following FXa-mediated PAR activation and investigated whether FXa

86 % clotting activity and reduced affinity for FXa membranes (approximately 20-fold) and did not bind t

87 utant had significantly reduced affinity for FXa.

88 important for FVIIa inhibition but also for FXa inhibition, i.e. for the transition of the loose to

89 The capacity for FXa to activate FVIII variants where cleavage at Arg(336

90 itically reduces the inhibition constant for FXa to below the plasma concentration of TFPI.

91 e incubation mixtures were immunoblotted for FXa product.

92 o unveil a high affinity binding site(s) for FXa.

93 n the serpin that is an interactive site for FXa in the complex.

94 values for the interaction of rTAP with four FXa mutants (Tyr(99) --> Thr, Phe(174) --> Asn, Arg(143)

95 ependent factor Xa (FXa) generation and free FXa.

96 a TF-FVIIa mutant complex with impaired free FXa generation but activating both FVIII and FIX support

97 s are activated to produce its cofactor FVa, FXa(I16L) is driven to the protease state and restores h

98 6PS) triggers assembly of a fully active FVa-FXa complex in solution and (2) that 2 molecules of C6PS

99 Ca(2+) to show that the apparent K(d) of FVa-FXa interaction increased with an increase in FXa concen

100 that are selectively activated by TF:FVIIa, FXa, and thrombin.

101 ocked PAR activation by the ternary TF-FVIIa-FXa complex but not by the non-coagulant TF-FVIIa binary

102 and IX through the formation of the TF-FVIIa-FXa-TFPI complex.

103 activity and the colocalization of TF-FVIIa-FXa-TFPI with caveolin-1.

104 a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with th

105 determined the proteolytic activity of human FXa toward human Pre2 as a substrate both at fixed membr

106 required to explore the potential use of IgG FXa reactivity as a novel biomarker to stratify treatmen

107 In FXa-catalyzed prothrombin activation assays, both FV and

108 This loop is highly acidic in FXa, containing three Glu residues at positions 36, 37,

109 to heparin (K(D) ~ 20 nM), but no change in FXa inhibition was observed in the presence of the cofac

110 ing and enhancement of TFPI was confirmed in FXa inhibition assays and using surface plasmon resonanc

111 loro- versus methyl-substituted P1 groups in FXa, which extends beyond the current series.

112 Xa interaction increased with an increase in FXa concentration at 5 mM Ca(2+), but the K(d) was only

113 conclusion, PAR-1 and PAR-2 are involved in FXa-mediated intracellular Ca(2+) release in HUVEC and F

114 This loop in FXa is highly acidic and contains three Glu residues at

115 n the absence of PS, whereas the response in FXa inhibition produced by PS was reduced with TFPI(K3P1

116 d the FV acidic region, which is retained in FXa-activated FVa and platelet FVa.

117 activators, but it plays no apparent role in FXa recognition of the cofactor in the prothrombinase co

118 olytic activity and formation of an inactive FXa dimer in solution.

119 branes also trigger formation of an inactive FXa dimer.

120 APS-IgG and SLE/APS- IgG increased FXa mediated NFkappaB signalling and this effect was ful

121 tes TFPI and ADTRP expression, and increases FXa inhibition by TFPI in an ADTRP- and caveolin-1-depen

122 .04, when FXa/FVa is 1:4, with an increasing FXa and substrate concentration.

123 at fixed membrane concentration (increasing FXa concentration) and at fixed FXa concentration (incre

124 Desmolaris also inhibits FXa with lower affinity, independently of protein S.

125 s FVIIa and the K2 domain similarly inhibits FXa.

126 , we report that TIX-5 specifically inhibits FXa-mediated FV activation involving the B domain of FV

127 x, but did not affect formation of the loose FXa-TFPI complex.

128 urther that the enhancement of TFPI-mediated FXa inhibition by protein S and FV depends on a direct p

129 ugh FV alone did not influence TFPI-mediated FXa inhibition, it further enhanced TFPI in the presence

130 We monitored FXa activity at 5, 20, and 50 nM FXa while titrating wit

131 transition in factor X through mutagenesis (FXa(I16L) and FXa(V17A)) not only alters active site fun

132 A mutant FXa (R165A) that has reduced prothrombinase activity sho

133 but preserving FVIIIa generation by nascent FXa, can support intrinsic pathway coagulation.

134 Moreover, nascent FXa product of TF-FVIIa can transiently escape the slow

135 A mixture of 50 nM FXa and 50 nM FVa in the presence of 400 muM C6PS yielde

136 e monitored FXa activity at 5, 20, and 50 nM FXa while titrating with FVa in the presence of 400 muM

137 Xa homodimers and Xa.Va heterodimers, but no FXa dimers bound to FVa.

138 ing loop mutant in which residues 220-225 of FXa were replaced with the corresponding residues of thr

139 The ability of FXa(I16L) to reverse the anticoagulant effects of FXa in

140 nd to enhance both the catalytic activity of FXa and the cofactor activity of FVa.

141 ke other serpins to regulate the activity of FXa but in a manner uniquely dependent on protein Z, pro

142 Alteration of FXa zymogenicity yields variants (V17M, I16L, I16M, V17T

143 Notably, assembly of FXa(I16L) and FXa(V17A) on activated platelets with fact

144 Binding of FXa active site-labeled with Oregon Green to FV and FVa

145 This new class of FXa variants provides a useful and flexible platform for

146 The combination of FXa and FVIIa maximally enhanced infection for TF(+)/gC(

147 specifically investigate the contribution of FXa and thrombin, mice were fed chow containing either r

148 nt, unlike the strict membrane dependence of FXa for high affinity FVa binding.

149 odel that takes into account dimerization of FXa after binding to a membrane, which yielded estimates

150 Here we ask whether dimerization of FXa and its binding to FVa in the presence of C6PS are c

151 ombinase assembly and possible disruption of FXa inhibition by the tissue factor pathway inhibitor.

152 are both located in the catalytic domain of FXa and that these sites are linked thermodynamically.

153 ally, TF or gC partly enhanced the effect of FXa, but not FVIIa, revealing gC as a novel PAR2 cofacto

154 16L) to reverse the anticoagulant effects of FXa inhibitor depends, at least in part, on the ability

155 APS patients and investigated the effects of FXa-reactive mAb on AT inactivation of FXa.

156 a TFPI cofactor, enhancing the efficiency of FXa inhibition.

157 conclude that the PS-mediated enhancement of FXa inhibition by TFPI-alpha involves an interaction bet

158 istence of a membrane-bound inactive form of FXa.

159 esis showed that the GLA-EGF(NC) fragment of FXa (lacking the catalytic domain) neither dimerized nor

160 ACH-11 inhibited the catalytic function of FXa towards its substrate S-2222 via a mixed model with

161 cells with FXIa increased the generation of FXa and promoted TF-dependent fibrin formation in recalc

162 n III, and 2 of 10 inhibited inactivation of FXa by antithrombin III.

163 ts of FXa-reactive mAb on AT inactivation of FXa.

164 to FXa and interfere with AT inactivation of FXa.

165 b significantly inhibited AT inactivation of FXa.

166 Xa also enhanced TFPI-mediated inhibition of FXa approximately 12-fold in the presence of protein S.

167 observed for the PZ-dependent inhibition of FXa by ZPI.

168 d enhancement of TFPI-mediated inhibition of FXa compared with free protein S.

169 a binding to FIXa as judged by inhibition of FXa generation performed in the absence of vesicles (K(i

170 FV could enhance TFPI-mediated inhibition of FXa in the presence of protein S, suggesting a functiona

171 Unlike inhibition of FXa, inhibition of FIXa did not strictly require protein

172 The fluorescence lifetime of FXa labeled in its active sites with a dansyl fluorophor

173 identified Arg(150) on the autolysis loop of FXa as a candidate residue that may specifically interac

174 was replaced with the corresponding loop of FXa.

175 tivity of AT with the sodium loop mutants of FXa in the absence of the cofactor was severely impaired

176 ial cell surface regulates the production of FXa by inhibiting the TF/VIIa complex.

177 DeltaK3) produced comparable prolongation of FXa-induced coagulation in PS-deficient plasma, but the

178 heparin-mediated enhancement in the rate of FXa inhibition by ZPI was reduced to ~30-fold for ZPI-3A

179 approximately 4-6-fold increases in rates of FXa-catalyzed inactivation of FVIIIa, which paralleled t

180 1-41) of FIXa with corresponding residues of FXa renders the FIXa chimera susceptible to inactivation

181 The K(d')s of FXa binding with rFVa (wild-type, C2 mutant, C1 mutant,

182 rily responsible for its high specificity of FXa inhibition by a slow- and tight-binding mechanism.

183 ine with this, irreversible stabilization of FXa(I16L) with Glu-Gly-Arg-chloromethyl ketone fully res

184 factor IXa binding, and platelet support of FXa generation, suggesting the importance of both releas

185 oximine (+)-1j in an asymmetric synthesis of FXa inhibitor F.

186 ing with the anticoagulant function of AT on FXa in some APS patients.

187 Three other surface loops on FXa including 39, 60, and the sodium-binding 220 loops h

188 -l-serine (C6PS), binds to discrete sites on FXa, FVa, and prothrombin to alter their conformations,

189 sence of calcium, C6PS binds to two sites on FXa, one in the epidermal growth factor-like (EGF) domai

190 n of baboon serum with thrombin, plasmin, or FXa did not show noticeable complement cleavage unless s

191 t cannot be cleaved/activated by thrombin or FXa also enhanced TFPI-mediated inhibition of FXa approx

192 used with factor Xa (FXa) and phospholipids (FXa/phosphatidylcholine-phosphatidylserine [PCPS]) vs LD

193 In hemophilic plasma, FXa(I16L) and FXa(V17A) have prolonged half-lives compar

194 cing a strong burst of thrombin and plasmin, FXa/PCPS infusion did not produce measurable levels of c

195 tification of compound 20 as the most potent FXa inhibitor in this series (IC(50) = 2.4 nM, EC(2xPT)

196 bin to alter their conformations, to promote FXa dimerization (K(d) ~ 14 nM), and to enhance both the

197 tor Xa mutants with zymogen-like properties (FXa(I16L) and FXa(V17A)) circumvent these limitations.

198 ase, a complex consisting of serine protease FXa and cofactor FVa, anchored to anionic phospholipids

199 This was confirmed in purified FXa inhibition assays in which no protein S enhancement

200 VII (TF-FVIIa) via formation of a quaternary FXa-TFPI-TF-FVIIa complex.

201 8, 92, and 128 nM for 5, 20, and 50 nM R165A FXa, respectively).

202 Antagonism of PAR-1 and PAR-2 reduced FXa-induced Ca(2+) release.

203 roquine or fluvastatin significantly reduced FXa-induced and IgG-potentiated Ca(2+) release.

204 ning a mutation in the heparin-binding site (FXa-R240A) was minimally affected by heparin.

205 Importantly, three of six FXa-reactive mAb significantly inhibited AT inactivation

206 sence of anionic membranes as it binds snake-FXa with high affinity in solution.

207 Treatment with a specific FXa inhibitor, hydroxychloroquine or fluvastatin signifi

208 506, Arg-306, and other previously suggested FXa binding sequences, delineate a continuous surface on

209 thrombinase complex on the platelet surface, FXa cleaves ProT at Arg-271, generating the inactive pre

210 n emerges as an atypical serpin that targets FXa and displays unique phospholipid specificity.

211 Our data indicate that TF, FXa, and thrombin differentially contribute to vascular

212 effectively prevented inhibition of FVIIa/TF/FXa and improved clot formation in hemophilia blood and

213 Ia (FVIIa)/tissue factor/Factor Xa (FVIIa/TF/FXa).

214 smon resonance experiments demonstrated that FXa bound TFPI(WT) and TFPI-(DeltaK3) but not the isolat

215 n involving the B domain of FV and show that FXa activation of FV is pivotal for plasma and blood clo

216 ing mouse models of hemophilia, we show that FXa(I16L) has a longer half-life than wild-type FXa and

217 using human or murine analogs, we show that FXa(I16L) is more efficacious than FVIIa, which is used

218 The FXa variants were remarkably effective in mouse injury m

219 In contrast, the FXa-catalyzed hydrolysis of N-alpha-Z-D-Arg-Gly-Arg-pNA.

220 On the other hand, the FXa mutant interacted with factor Va with a normal appar

221 required to understand the structure of the FXa dimer or the FXa-FVa complex.

222 o a membrane, which yielded estimates of the FXa dimerization constant on a membrane as well as the k

223 ion of these loops to the specificity of the FXa interaction with activated AT, several loop mutants

224 ion could merely represent inhibition of the FXa product whose activity was measured, inhibition of F

225 loops play a role in the specificity of the FXa-AT interaction; however, neither loop specifically i

226 ng in a "common" pathway at the level of the FXa/FVa (prothrombinase) complex.

227 rstand the structure of the FXa dimer or the FXa-FVa complex.

228 NotD binds specifically to the FXa binding site expressed on factor V (FV) upon activat

229 In the absence of factor Va, the FXa variants are poor enzymes for a range of physiologic

230 hy, and showed an extensive overlap with the FXa contact region highlighting a structural basis for i

231 ented transition from the loose to the tight FXa-TFPI complex, but did not affect formation of the lo

232 for the transition of the loose to the tight FXa-TFPI complex.

233 the fluorescence of fluorescein attached to FXa's active site serine was depolarized in a FXa concen

234 d that some thrombin-reactive Ab may bind to FXa and interfere with AT inactivation of FXa.

235 competitive, reversible and tight binding to FXa (picomolar range).

236 rome (APS) display higher avidity binding to FXa with greater coagulant effects compared to systemic

237 ix of six thrombin-reactive IgG mAb bound to FXa and that the levels of plasma IgG anti-FXa Ab in 38

238 FVa709, FVa699, FVa692, and FVa678 bound to FXa membranes and thrombin-agarose in a manner that was

239 e-chain B-domain-truncated factor V bound to FXa membranes with an affinity that was identical to fac

240 esis that FVa residues 499-505 contribute to FXa binding, we created the FVa loop swap mutant (design

241 Relative to FXa, AT inhibits FIXa with approximately 40-fold slower

242 quence alignments indicated that, similar to FXa, residue 36 is a Glu in both mouse and bovine FIXa a

243 rypsin-like serine proteases (thrombin, tPA, FXa, plasmin, plasma kallikrein, trypsin, FVIIa).

244 (I16L) has a longer half-life than wild-type FXa and does not cause excessive activation of coagulati

245 d better catalytic efficiency than wild-type FXa in the absence of factor Va.

246 tivation, paradoxically allowing uninhibited FXa to persist in plasma.

247 uding that of the most zymogen-like variant (FXa-I16T), was greatly enhanced when bound to FVa membra

248 that a novel zymogen-like factor Xa variant (FXa-I16L) was effective in correcting the coagulation de

249 In vitro, FXa stably associated with TF-FVIIa activates FVIII, but

250 verse, 0.30 +/- 0.05 and 0.19 +/- 0.04, when FXa/FVa is 1:4, with an increasing FXa and substrate con

251 ations > 5 Km, the KSIE is 1.6 +/- 0.3, when FXa is in a 1:1 ratio with FVa but becomes increasingly

252 edominance of the meizothrombin pathway when FXa is well-saturated with the prothrombin complex.

253 ated PAR activation and investigated whether FXa reactive IgG from patients with APS or SLE/APS- alte

254 ived monoclonal IgG antiphospholipid Ab with FXa and the presence of IgG anti-FXa Ab in APS patients

255 Thrombin combined with FXa/FVIIa enhanced infection, suggesting that PAR1 and P

256 The BR competes with FXa for binding to FV(a), and limited proteolysis of the

257 rom ZPI once ZPI forms a stable complex with FXa, and kinetic analyses confirmed that PZ acted cataly

258 main enables TFPI to interact optimally with FXa on a phospholipid membrane.

259 utants exhibited near normal reactivity with FXa and FXIa in the absence of cofactors and in the pres

260 in when the variant was fully saturated with FXa membranes.

261 or myocardial infarction with DTIs than with FXa inhibitors.

262 a novel biomarker to stratify treatment with FXa inhibitors in these patients.

263 reversible inhibitor of activated factor X (FXa) and also inhibits the FVIIa-TF complex.

264 idering that activated coagulation factor X (FXa) is homologous to thrombin in the catalytic domains

265 ociation with the enzyme activated factor X (FXa) to form the prothrombinase complex is a pivotal ini

266 inhibitor that inhibits activated factor X (FXa) via a slow-tight binding mechanism and tissue facto

267 is a well-characterized activated factor X (FXa)-dependent inhibitor of TF-initiated coagulation pro

268 bound to the activated coagulation factor X (FXa).

269 mbin and the activated coagulation factor X (FXa).

270 rating the inhibition of activated factor X (FXa).

271 inhibit the activity of activated factor X (FXa); however, neither inhibitor exhibits any reactivity

272 e show that activated coagulation factors X (FXa) or VII (FVIIa) directly affect HSV1 infection of hu

273 f the serpin with factors IXa (FIXa) and Xa (FXa), thereby improving the rate of reactions by 300- to

274 logous to coagulation factors V (FV) and Xa (FXa).

275 lly pliant variant of coagulation factor Xa (FXa(I16L)) rendered partially inactive by a defect in th

276 Here we found that factor Xa (FXa) activated PAR1 at canonical Arg41 similar to thromb

277 e, plasma concentration, and anti-Factor Xa (FXa) activity and compared efficacy and safety outcomes

278 er of highly selective and potent factor Xa (FXa) and FIXa inhibitors were identified by simple switc

279 a, C5b-9) in baboons infused with factor Xa (FXa) and phospholipids (FXa/phosphatidylcholine-phosphat

280 ts rate of complex formation with factor Xa (FXa) by 200-300-fold.

281 S (PS) enhances the inhibition of factor Xa (FXa) by tissue factor pathway inhibitor-alpha (TFPI-alph

282 bit both TF-factor VIIa-dependent factor Xa (FXa) generation and free FXa.

283 Factor Xa (FXa) has a prominent role in amplifying both inflammatio

284 Factor Xa (FXa) has materialized as a key enzyme for the interventi

285 r snake, Notechis scutatus, and a factor Xa (FXa) homolog.

286 The molecular mechanism of factor Xa (FXa) inhibition by Alboserpin, the major salivary gland

287 ct thrombin inhibitors (DTIs) and factor Xa (FXa) inhibitors, are emerging alternatives for prophylax

288 osphatidylserine (C6PS) to bovine factor Xa (FXa) leads to Ca2+-dependent dimerization in solution.

289 Direct inhibitors of coagulation factor Xa (FXa) or thrombin are promising oral anticoagulants that

290 w- and tight-binding inhibitor of factor Xa (FXa) with a reported equilibrium dissociation constant (

291 membrane-dependent interaction of factor Xa (FXa) with factor Va (FVa) forms prothrombinase and drive

292 t isotope effects (KSIEs) for the factor Xa (FXa)-catalyzed activation of prothrombin in the presence

293 nt anticoagulant role through the factor Xa (FXa)-dependent inhibition of tissue factor/factor VIIa.

294 ical process culminating with the factor Xa (FXa)-mediated conversion of the prothrombin (ProT) zymog

295 t to an active cofactor (FVa) for factor Xa (FXa).

296 se inhibitor (ZPI) inhibition of factors Xa (FXa) and XIa (FXIa) by a template mechanism.

297 t regulator of blood coagulation factors Xa (FXa) and XIa.

298 ial assembly of a membrane-associated PZ-ZPI-FXa Michaelis complex (K(M) 53+/-5 nM) followed by conve

299 5 nM) followed by conversion to a stable ZPI-FXa complex (k(lim) 1.2+/-0.1 s(-1)).

300 The ZPI-FXa complex was only transiently stable and dissociated