ライフサイエンスコーパス: factor IXa

1 d this subpopulation of platelets also bound factor IXa.

2 ows significant thrombin generation only for factor IXa.

3 ition of the target proteases, factor Xa and factor IXa.

4 nhancements in reactivity with factor Xa and factor IXa.

5 ivation of factor VII by IIa, factor Xa, and factor IXa.

6 as the binding of factor VIII light chain to factor IXa.

7 f factor VIIIa were implicated in binding to factor IXa.

8 c helical peptides in supporting function of factor IXa.

9 scence anisotropy of fluorescein-Phe-Phe-Arg factor IXa.

10 509) blocked the A2-dependent stimulation of factor IXa.

11 residues in stabilizing A2 association with factor IXa.

12 the appropriate position for the binding of factor IXa.

13 entified the A2 558-loop as interacting with factor IXa.

14 let receptor-mediated factor X activation by factor IXa.

15 sed by steric hindrance for interaction with factor IXa.

16 IIIaXa molecules in the preparation can bind factor IXa.

17 ude lower than that of recombinant wild-type Factor IXa.

18 d, active-site-blocked derivative of porcine factor IXa.

19 increase in the affinity of factor VIIIa for factor IXa.

20 his effect involves allosteric modulation of factor IXa.

21 tor with the target proteases, factor Xa and factor IXa.

22 n-activated variants with both factor Xa and factor IXa.

23 tivated antithrombin with both factor Xa and factor IXa.

24 s and the kinetics of factor X activation by factor IXa.

25 the occupancy of three receptors: (1) enzyme factor IXa, (2) cofactor factor VIII(a), and (3) substra

26 (V(max) 2.90 +/- 0.37 pM/min) versus normal factor IXa (37.6 +/- 0.15 pM/min) was due to its decreas

27 In the presence of active site-inhibited factor IXa (4 nM) and factor II (4 microM), factor X bin

28 nds in the presence of active site-inhibited factor IXa (45 nM) and 5 mM CaCl(2).

29 tic complex composed of the serine protease, factor IXa, a protein cofactor, factor VIIIa, a phosphol

30 ced function involve condensation of enzyme (factor IXa), activated cofactor (factor VIIIa), and subs

31 ding sites but less than 10% of factor VIIIa-factor IXa activating activity.

32 The aptamer completely blocks factor IXa activation of factor X regardless of the pres

33 hat it contributes to the orientation of the factor IXa active site and its relation to substrate.

34 anced by EGR-chloromethylketone bound to the factor IXa active site or addition of factor X, and redu

35 was prepared by covalent modification of the Factor IXa active site.

36 factors IXa and X resulted in an increase in factor IXa activity because of conversion of the HC to A

37 hieving inhibition and active restoration of factor IXa activity in combination with platelet-directe

38 n of the A2 subunit-dependent stimulation of factor IXa activity, suggesting that factor IXa-interact

39 apacity for isolated A2 subunit to stimulate factor IXa activity, we show that a panel of these inhib

40 have reduced helical content, do not support factor IXa activity.

41 eliminated the A1-dependent contribution to factor IXa activity.

42 inimal differences in kinetic parameters and factor IXa affinity for E113A and wild-type factor VIIIa

43 t (if any) on thrombin generation induced by factor IXa alone.

44 ease in kcat of over 1000-fold compared with factor IXa alone.

45 s of factor IX zymogen, factor IX alpha, and factor IXa alpha were similar: 0.38 +/- 0.02 s(-1), 0.34

46 a cleavage rates of free factor IX alpha and factor IXa alpha with that of factor IX zymogen.

47 VIII molecule, such as the binding-sites for factor IXa and activated protein C; it has also allowed

48 nthetic peptide comprising the Gla domain of factor IXa and antibodies directed to the Gla domain of

49 eak initial enzyme-inhibitor complex between factor IXa and basic pancreatic trypsin inhibitor that i

50 this preference for inhibiting thrombin over factor IXa and factor VIIa increased to 17-300-fold, sug

51 In the presence of active site-inhibited factor IXa and factor VIIIa there are two independent fa

52 gamma-carboxyglutamic acid (Gla) domains of factor IXa and factor X since (i) a synthetic peptide co

53 s of fVIIIa cofactor activity using purified factor IXa and factor X suggested this difference is due

54 In addition, the K(d)s of factor IXa and factor X were lower for phospholipid vesi

55 o effectively scavenge the limited traces of factor IXa and factor Xa formed in the presence of TFPI.

56 ated A2 subunit modulates the active site of factor IXa and identifies a functional role for this sub

57 able complexes with thrombin, factor Xa, and factor IXa and inhibit these proteases with stoichiometr

58 novel platform of anticoagulation targeting factor IXa and its active reversal to percutaneous coron

59 The aptamer binds tightly to factor IXa and prolongs the clotting time of human plasm

60 pecific antibody recognizing both the enzyme factor IXa and the substrate factor X.

61 d normally by factor VIIa and tissue factor, factors IXa and VIIIa, and Russell's viper venom.

62 However, extended reaction of HC with factors IXa and X resulted in an increase in factor IXa

63 ssive enhancements in rates of inhibition of factors IXa and Xa (114- and 110-fold, respectively), bu

64 n) initiated with the same concentrations of factors IXa and Xa and thrombin.

65 arge increases in the rates of inhibition of factors IXa and Xa but not of thrombin.

66 y of antithrombin with coagulation proteases factors IXa and Xa by 300- to 600-fold through a conform

67 proteolytic cleavage by thrombin, factor Xa, factor IXa, and activated protein C can lead to inactiva

68 gin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence re

69 he direct inhibition of thrombin, factor Xa, factor IXa, and factor VIIa by CDSO3, FDSO3, and SDSO3,

70 ated inactivation of IIa, mIIa, factor VIIa, factor IXa, and factor Xa; (c) the initial activation of

71 y hamster kidney cell-expressed factor VIII, factor IXa, and phospholipid vesicles to determine the i

72 aptamer that specifically binds and inhibits factor IXa, and RB007 (antidote), the complementary olig

73 1 and 2 (Cys88-Cys109) of the EGF2 domain of factor IXa are essential for normal interactions with th

74 gonucleotides (aptamers) against coagulation factor IXa are potent anticoagulants.

75 bunit (an effect retarded in the presence of factor IXa), as well as abrogating protective interactio

76 A model is proposed for FVIIIa and factor IXa assembly within the membrane-bound factor X-a

77 ge by thrombin, factor VIIIa associates with factor IXa at the surface of activated platelets or endo

78 d (iii) heparin bridging of antithrombin and factor IXa augmented by calcium ions (130-1000-fold depe

79 a new sensitive method for the detection of factor IXa based on its affinity to antithrombin III.

80 whereas inhibition by active site-inhibited factor IXa beta was competitive (Ki 0.33 +/- 0.05 microM

81 e in calcium transients by 15 s and positive factor IXa binding by 2 min, with calcium transients sus

82 Annexin V decreased factor IXa binding in the presence or absence of factor

83 oximately 250 each/platelet): (1) a specific factor IXa binding site requiring the intact EGF2 domain

84 factor IX, which blocks the shared factor IX/factor IXa binding site, the substrate, factor X, and th

85 DTA for 5-20 min before addition of calcium, factor IXa binding sites developed on a smaller subpopul

86 onclude that PAR-1-stimulated development of factor IXa binding sites in a subpopulation of platelets

87 mined the density of high affinity saturable factor IXa binding sites to be 500-600 sites/platelet.

88 imulated platelets expose approximately 6000 factor IXa binding sites/platelet.

89 1, S3-L6, and F9-Q11) acted alone to inhibit factor IXa binding to approximately 50% of the 500-600 s

90 DHG competed factor IXa binding to immobilized LMWH with an EC(50) 35

91 were screened for their capacity to inhibit factor IXa binding to platelets.

92 Factor IXa binding to the activated platelet surface is

93 pulation with pronounced calcium transients, factor IXa binding, and platelet support of FXa generati

94 ce density as seen in platelets negative for factor IXa binding.

95 (Active site-modified) factor IXa, blocked cleavage at the A2 site.

96 Factor IXa bound LMWH with significantly higher affinity

97 ays clotting of plasma initiated by purified factor IXa but has much less of an effect on clotting in

98 300-500-fold), (ii) allosteric activation of factor IXa by calcium ions (4-8-fold), and (iii) heparin

99 All seven mutants were similar to the native factor IXa by SDS-PAGE, active site titration, and conte

100 f their AP, and 2) expected trace amounts of factor IXa can trigger thrombin generation in the absenc

101 at isolated A2 subunit enhanced the kcat for factor IXa-catalyzed activation of factor X by approxima

102 c levels ( approximately 100 nM) potentiates factor IXa-catalyzed activation of factor X on both acti

103 ses limited cofactor activity in stimulating factor IXa-catalyzed activation of factor X.

104 nits, increases the catalytic efficiency for factor IXa-catalyzed activation of factor X.

105 examined for their ability to accelerate the factor IXa-catalyzed activation of factor X.

106 Although the isolated A2 subunit stimulates factor IXa-catalyzed generation of factor Xa by approxim

107 an approximately 4-fold greater affinity for factor IXa compared with factor VIIIa wild type in react

108 suggest that activation of the factor VIIIa-factor IXa complex can result from binding of individual

109 factor VIII or function of the factor VIIIa-factor IXa complex even when PE and phosphatidylcholine

110 is due to a requirement of the factor VIIIa-factor IXa complex for unsaturated acyl chains that exce

111 S) increase the activity of the factor VIIIa-factor IXa complex in a biphasic manner with half-maxima

112 r activation of factor X by the factor VIIIa-factor IXa complex was 1700 nM in solution, 70-fold high

113 than 5% normal activity of the factor VIIIa-factor IXa complex.

114 inding sites or to activate the factor VIIIa-factor IXa complex.

115 s for factor IX being about half of that for factor IXa, consistent with previous equilibrium binding

116 a proceeded at a similar rate independent of factor IXa, consistent with the location of the preferen

117 We conclude that the Gla domain (G4-Q11) of factor IXa contains two conformationally constrained loo

118 the presence or absence of factor VIIIa, and factor IXa could also decrease annexin V binding on some

119 scence anisotropy of fluorescein-Phe-Phe-Arg-factor IXa (Deltar = 0.015) and markedly increased aniso

120 thway of coagulation, targeted inhibition of Factor IXa-dependent coagulation might inhibit microvasc

121 d using a protein-binding oligonucleotide to factor IXa (drug, RB006) and its complementary oligonucl

122 erotrimer, which functions as a cofactor for factor IXa during intrinsic pathway factor X activation.

123 branes increase the kcat of the factor VIIIa-factor IXa enzyme complex by more than 1000-fold.

124 tor IXa-factor VIIIa) via interaction with a factor IXa exosite.

125 ted to functional inhibition of factor VIIIa-factor IXa (factor Xase) enzyme complex.

126 und factor IX and approximately 50% of bound factor IXa, factor IX was ineffective (at > 1000-fold mo

127 tivator of factor X consists of a complex of factor IXa, factor VIIIa, Ca(2+) and a suitable phosphol

128 siological concentrations, concentrations of factor IXa, factor Xa, and thrombin were set either equa

129 LMWH induced a modest decrease in factor IXa-factor VIIIa affinity [K(D(app))] on PL vesic

130 A demonstrated a 4-fold increase in apparent factor IXa-factor VIIIa affinity and dramatically increa

131 rast, LMWH caused a substantial reduction in factor IXa-factor VIIIa affinity in the presence of C6PS

132 Likewise, factor IXa H92A and K241A showed factor IXa-factor VIIIa affinity similar to factor IXa w

133 gonizes cofactor activity without disrupting factor IXa-factor VIIIa assembly on the PL surface.

134 ISIS 2302 modestly decreased the affinity of factor IXa-factor VIIIa binding in the presence of phosp

135 the factor VIIa-tissue factor complex or the factor IXa-factor VIIIa complex and then to function as

136 ated from the system, no contribution of the factor IXa-factor VIIIa complex to factor X activation w

137 x(app) varied in proportion to the predicted factor IXa-factor VIIIa concentration.

138 r LMWH and factor VIIIa, disrupting critical factor IXa-factor VIIIa interactions.

139 lar weight heparin (LMWH) was independent of factor IXa-factor VIIIa membrane assembly.

140 an plasma by inhibition of intrinsic tenase (factor IXa-factor VIIIa) activity.

141 nhibition was dependent on intrinsic tenase (factor IXa-factor VIIIa) components.

142 parin inhibits the intrinsic tenase complex (factor IXa-factor VIIIa) via interaction with a factor I

143 of factor X activation by intrinsic tenase (factor IXa-factor VIIIa) was investigated.

144 activation by the intrinsic tenase complex (factor IXa-factor VIIIa).

145 s indicates that in the presence of TFPI the factor IXa.factor VIIIa pathway becomes essential at low

146 During blood coagulation, factor IXa (FIXa) activates factor X (FX) requiring Ca2+

147 pidermal growth factor (EGF2)-like domain of factor IXa (FIXa) are important for assembly of the fact

148 Interestingly, factor IXa (FIXa) binding affinity for WT FVIIIa was sig

149 This loop in factor IXa (FIXa) has 3 basic residues (Arg143, Lys147,

150 n as the pro-cofactor to the serine-protease Factor IXa (FIXa) in the FVIIIa-FIXa complex assembled o

151 A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of

152 Blood coagulation factor IXa (fIXa) is a trypsin-like serine protease with

153 Factor IXa (FIXa) is known to have a binding site for he

154 ctivation require occupancy of receptors for factor IXa (FIXa), factor VIII (FVIII), and FX on the ac

155 factor X (FX) activation require binding of factor IXa (FIXa), factor VIII(a) [FVIII(a)], and FX to

156 oarray of potential aptamers for the protein factor IXa (fIXa).

157 ite-dependent interaction of the serpin with factors IXa (FIXa) and Xa (FXa), thereby improving the r

158 All of them, including factors IXa (FIXa), FXa/FX, FVa, FVIII, prothrombin, and

159 A competitive inhibitor of native Factor IXa for assembly into the intrinsic Factor X acti

160 fIX(G4)(-)(Q11) competes with factor IXa for binding sites on phosphatidylserine-conta

161 omplex formation; PE lowers the K(d(app)) of factor IXa for both phospholipid/Ca(2+) and phospholipid

162 at (a) PL increases the apparent affinity of factor IXa for factor VIIIa approximately 2,000-fold, an

163 pproximately 8-fold reduction in affinity of factor IXa for factor VIIIa.

164 IXa-phospholipid but reduced the affinity of factor IXa for factor VIIIa.

165 ond epidermal growth factor (EGF2) domain of factor IXa for platelet binding and catalysis, a chimeri

166 tor IX specifically increase the affinity of factor IXa for the intrinsic factor X activation complex

167 though factor VIIIa improved the affinity of factor IXa for the lipid surface from Kd approximately 6

168 d distinct from the site used by the enzyme, factor IXa, for assembly of the factor X activating comp

169 Blood coagulation factor IXa gains proteolytic efficiency upon binding to

170 The rate of factor IXa generation catalyzed by FXIa was unaffected b

171 for LMWH was increased less than 2-fold for factor IXa H92A and K241A but over 3.5-fold for factor I

172 Likewise, factor IXa H92A and K241A showed factor IXa-factor VIIIa

173 An aptamer targeting factor IXa has been evaluated in animal models and sever

174 Blood coagulation factor IXa has been presumed to be regulated by the serp

175 contribution to the protease specificity of factor IXa has not been studied.

176 These data support the role of the factor IXa heparin-binding exosite as a critical regulat

177 trinsic tenase components, and establish the factor IXa heparin-binding exosite as the relevant molec

178 The role of the factor IXa heparin-binding exosite in coagulation was as

179 These results suggest that the factor IXa heparin-binding exosite participates in both

180 results implicate Lys(98) and the 99-loop of factor IXa in defining enzyme inhibitor specificity.

181 e aptamer binding to the catalytic domain of factor IXa in such a way as to block an extended substra

182 Submicellar C6PS enhanced activity of factor IXa in the absence of factor VIIIa, but the effec

183 antithrombin is essentially unreactive with factor IXa in the absence of heparin (k(ass) approximate

184 03)(-23), enhances proteolytic efficiency of factor IXa in the absence of phospholipid membranes.

185 bin reactivity with thrombin, factor Xa, and factor IXa in the absence or presence of heparin.

186 ity of factor VIII (FVIII) as a cofactor for factor IXa in the coagulation cascade is limited by its

187 ry to properly orient A2 subunit relative to factor IXa in the cofactor rather than directly stimulat

188 tor VIII (FVIII) functions as a cofactor for factor IXa in the contact coagulation pathway and circul

189 or VIII (fVIIIa) functions as a cofactor for factor IXa in the factor Xase complex.

190 ctor VIII (fVIII) functions as a cofactor of factor IXa in the intrinsic pathway of blood coagulation

191 scence anisotropy of fluorescein-Phe-Phe-Arg-factor IXa in the presence of factor X, whereas thrombin

192 in the 558-loop critical to interaction with factor IXa in Xase.

193 e level of chromogenic substrate cleavage by factor IXa increased more than 50-fold.

194 In the absence of TF, 5 to 100 pM of factor IXa increased thrombin generation to approach TF-

195 and antibodies directed to the Gla domain of factor IXa inhibit this acceleration, (ii) the accelerat

196 ble for enhancing the rates of factor Xa and factor IXa inhibition in the conformationally activated

197 Whether selective factor IXa inhibition produces an appropriate anticoagul

198 ither REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with ani

199 m, an RNA aptamer pair comprising the direct factor IXa inhibitor RB006 and its active control agent

200 The reversible factor IXa inhibitor REG1, as currently formulated, is a

201 esidues 558 to 565, previously shown to be a factor IXa interaction site.

202 mbin or factor Xa is essential to expose the factor IXa-interactive site(s) in the A2 subunit require

203 factor VIII residues 484-509 contribute to a factor IXa-interactive site.

204 tion of factor IXa activity, suggesting that factor IXa-interactive sites are masked in the A2 domain

205 e data, which indicate that the helix 330 of factor IXa interacts with the 558-565 region of the A2 s

206 a support a conclusion that the helix 330 of factor IXa interacts with the A2 558-565 sequence.

207 Ca2+ binding site in the protease domain of factor IXa involving Glu235 (Glu70 in chymotrypsinogen n

208 As Factor IXa is a key intermediary in the intrinsic pathwa

209 Thus, the intact EGF2 domain of factor IXa is critical for the formation of the factor X

210 olysis at Arg(336) by activated protein C or factor IXa is inactivating.

211 , heparin, but it has not been clear whether factor IXa is inhibited by the serpin with a specificity

212 Factor VIIIa, the protein cofactor for factor IXa, is comprised of A1, A2, and A3-C1-C2 subunit

213 Factor VIIIa, the protein cofactor for factor IXa, is comprised of A1, A2, and A3-C1-C2 subunit

214 ffinity membrane binding of factor VIIIa and factor IXa, it is not known whether PS is the lipid that

215 surface (K(d) 64.7 +/- 3.9 nM) versus normal factor IXa (K(d) 1.21 +/- 0.07 nM), resulting in less bo

216 ibition of chromogenic substrate cleavage by factor IXa (K(I) = 88 nM).

217 Factor IXa K126A, N129A, and K132A demonstrated modest r

218 cofactor factor VIIIa, compared with native factor IXa (Kd(app)FIXa approximately 1.1 nm, Vmax appro

219 factor VIIa-tissue factor (Ki = 1.6 microM), factor IXa (Ki = 206 nM), factor Xa (Ki = 364 nM), and f

220 ), and 240 nM (F9-Q11), compared with native factor IXa (Ki approximately 2.5 nM).

221 elated with the effect of these mutations on factor IXa-LMWH affinity and the potency of LMWH for int

222 affinity analysis, and the K(D(app)) for the factor IXa-LMWH complex agreed with the K(I) for inhibit

223 g high affinity, saturable binding sites for factor IXa mediated by two disulfide-constrained loop st

224 s suggest that PS ODNs bind to an exosite on factor IXa, modulating catalytic activity of the intrins

225 However, the specific regions of the factor IXa molecule that are critical to this interactio

226 riments, we measured the affinities of these factor IXa molecules for a peptide comprising residues 5

227 In the absence of factor VIIIa, factor IXa N178A and R165A demonstrated a defective Vmax

228 latelets possess a specific binding site for factor IXa, occupancy of which has been correlated with

229 I (FVIIIa) forms a procoagulant complex with factor IXa on negatively charged membranes, including ac

230 II may result from its enhanced affinity for factor IXa on the physiological membrane.

231 mplex, and chromogenic substrate cleavage by factor IXa, only in the presence of ethylene glycol.

232 n contrast, the homologous clotting protease factor IXa or another endothelial cell ligand, fibrinoge

233 similarly-labeled derivatives of factor Xa, factor IXa, or factor VIIa did not alter the locations o

234 The effect of fVIII(2303)(-23) on factor IXa parallels the enhanced function produced by p

235 lf-life or chromogenic substrate cleavage by factor IXa-phospholipid but reduced the affinity of fact

236 col, the level of factor X activation by the factor IXa-phospholipid complex increased 3-fold, and th

237 ial inhibition of factor X activation by the factor IXa-phospholipid complex, and chromogenic substra

238 2 did not inhibit factor X activation by the factor IXa-phospholipid complex, or significantly affect

239 ely affected the interaction of heparin with factor IXa-phospholipid.

240 x agreed with the K(I) for inhibition of the factor IXa-PL complex by LMWH.

241 WH also inhibited factor X activation by the factor IXa-PL complex via a distinct mechanism that requ

242 The apparent affinity of LMWH for the factor IXa-PL complex was higher in the absence of facto

243 nhibit chromogenic substrate cleavage by the factor IXa-PL complex.

244 r X activation complex assembly, recombinant factor IXa point mutants in loop 1 (N89A, I90A, K91A, an

245 This organization of factor VIII allows the factor IXa protease and epidermal growth factor-like dom

246 ting with the heparin-binding exosite in the factor IXa protease domain, which disrupts interaction w

247 of the metabolites' binding affinity to the Factor IXa protein from the ALIS assay was completely co

248 e assembly of intrinsic tenase (factor VIIIa/factor IXa), prothrombinase (factor Va/factor Xa), and f

249 in apparent cofactor affinity (23-fold) for factor IXa R165, and an inability to stabilize cofactor

250 However, factor IXa R165A had a 65% reduction in the kcat for fac

251 Factor IXa R170A demonstrated a 2- to 3-fold increase in

252 In contrast, factor IXa R170A demonstrated a 4-fold increase in appar

253 tor IXa H92A and K241A but over 3.5-fold for factor IXa R170A, indicating that relative heparin affin

254 Factor IXa R233A demonstrated a 2.5-fold decrease in cof

255 in velocity index, whereas the response for factor IXa R233A was blunted and delayed relative to wil

256 We find that enhancement of factor IXa reactivity by enoxaparin is greatest for basi

257 Mutation of Lys(98) to Ala in factor IXa results in enhanced reactivity with all inhib

258 319 in the protease domain autolysis loop of factor IXa results in its diminished binding to factor V

259 PAR-1-stimulated platelets binds coagulation factor IXa, since confirmed by other laboratories.

260 tor is sterically hindered by the 99-loop of factor IXa, specifically residue Lys(98).

261 scence anisotropy of fluorescein-Phe-Phe-Arg factor IXa than that observed for A2 subunit alone and a

262 Thus, LMWH binds to an exosite on factor IXa that antagonizes cofactor activity without di

263 Thus, DHG binds to an exosite on factor IXa that overlaps with the binding sites for LMWH

264 nted with plasma-derived factor IX or 100 pM factor IXa, the EC(50) for DHG was similar.

265 y inhibit the interaction of A2 subunit with factor IXa, thus abrogating the contribution of this sub

266 nM in its presence, addition of annexin V to factor IXa titrations on lipid vesicles in the presence

267 V reduced the Vmax of factor X activation in factor IXa titrations on the platelet surface with an IC

268 ly, these results demonstrate the ability of factor IXa to be allosterically modulated by occupation

269 The ability of factor IXa to compete for physical assembly into the int

270 er, Kd,app of binding of active site-blocked factor IXa to factor VIIIa was calculated from its abili

271 Three inhibitor IgGs prevented binding of factor IXa to fVIII light chain, and the binding of each

272 t-dependent modulation of the active site of factor IXa to synergistically increase cofactor activity

273 prior to assembly with the serine protease, factor IXa, to form the factor X-activating enzyme (FX-a

274 by diminishing the catalytic activity of the factor IXa/VIIIa complex.

275 nt Kd for the interaction of A2 subunit with factor IXa was approximately 300 nM.

276 orescence anisotropy of fluorescein (Fl)-FFR-factor IXa was differentially altered by factor VIIIa tr

277 2 in chymotrypsin) of the protease domain of factor IXa was implicated in binding to factor VIIIa.

278 ase the rate of cleavage at the A2 site when factor IXa was present.

279 To evaluate interaction of FVIII with factor IXa, we performed an inhibition assay using a syn

280 All platelets binding factor IXa were positive for glycoprotein IX, at the sam

281 3)(-23) does not further enhance function of factor IXa when phospholipid vesicles are present.

282 s to promote the inhibition of factor Xa and factor IXa when the serpin is conformationally activated

283 factor IXa-factor VIIIa affinity similar to factor IXa wild type (WT).

284 or dramatically (R165A) reduced relative to factor IXa wild type.

285 ant proteases was reduced 20-30% relative to factor IXa wild type.

286 , the fVIIIaXa preparation bound dye-labeled factor IXa with 1:1 stoichiometry, indicating that all f

287 To define the role of this exosite, human factor IXa with alanine substituted for conserved surfac

288 anism for this inhibition, recombinant human factor IXa with alanine substituted for solvent-exposed

289 Reactivity of factor IXa with basic pancreatic trypsin inhibitor is en

290 Modeling studies of factor IXa with basic pancreatic trypsin inhibitor sugge

291 is of intrinsic tenase inhibition, employing factor IXa with mutations in the heparin-binding exosite

292 hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronar

293 We examined the reactivity of factor IXa with several isolated Kunitz-type inhibitor d

294 lly increased coagulant activity relative to factor IXa WT.

295 while urokinase, kallikrein, and coagulation factors IXa, Xa, XIa, and XIIa neither substantially act

296 ther supported by the normal k(cat) of bound factor IXa(Xegf2) (1701 min(-)(1)) indicating (1) an int

297 In kinetic studies, the decreased V(max) of factor IXa(Xegf2) activation of factor X on the platelet

298 The hypothesis that the binding defects of factor IXa(Xegf2) are the cause of the kinetic perturbat

299 t binding and catalysis, a chimeric protein (factor IXa(Xegf2)) was created by replacement of the EGF

300 ic site and (2) the normal behavior of bound factor IXa(Xegf2).