ライフサイエンスコーパス: factor Va

1 idylserine and binds prothrombinase (FITC Xa.factor Va).

2 ces thrombin by proteolytically inactivating factor Va.

3 iciency than wild-type FXa in the absence of factor Va.

4 se, it functioned in an equivalent manner to factor Va.

5 ne in the presence but not in the absence of factor Va.

6 n approximately 6-fold impaired affinity for factor Va.

7 actions that govern the eventual function of factor Va.

8 ranes with an affinity that was identical to factor Va.

9 egulated by (pro)exosite I interactions with factor Va.

10 the Arg506 scissile bond on the A2 domain of factor Va.

11 generation is the activation of factor V to factor Va.

12 g activity similar to the thrombin-activated factor Va.

13 elet-derived CKII phosphorylates coagulation factor Va.

14 th protein C inhibitor (PCI), and inactivate factor Va.

15 ctor Xa toward prothrombin in the absence of factor Va.

16 l role of the amino acid sequence 307-348 of factor Va.

17 vation of prethrombin 1 that is modulated by factor Va.

18 actor V affected APC inactivation of derived factor Va.

19 functional unit that has a binding site for factor Va.

20 4 inhibited protein S binding to immobilized Factor Va.

21 may compete for a Factor Xa binding site on Factor Va.

22 eled thrombin bound with similar affinity to factor Va.

23 s prothrombin to thrombin in the presence of factor Va.

24 with saturating concentrations of wild type factor Va.

25 tified on both the heavy and light chains of factor Va.

26 The binding of human factor Va(1) and factor Va(2) to 75:25 POPC/POPS vesicle

27 -activated factor Va exists as two isoforms, factor Va(1) and factor Va(2), which differ in the size

28 was approximately 3-fold higher than that of factor Va(1).

29 t of this, soluble C6PE binds to recombinant factor Va(2) (K(d) = approximately 6.5 mum) and to facto

30 The affinity of human factor Va(2) binding to POPC/POPS vesicles was approxima

31 of purified N2181Q were similar to those of factor Va(2) in prothrombinase assays carried out in the

32 The binding of human factor Va(1) and factor Va(2) to 75:25 POPC/POPS vesicles was also invest

33 prothrombinase complex between factor Xa and factor Va(2), compared with K(d)(app) for C6PS approxima

34 Va exists as two isoforms, factor Va(1) and factor Va(2), which differ in the size of their light ch

35 rombinase activity in the presence of excess factor Va (20 nM).

36 assembled with saturating concentrations of factor Va(3K) had a 6-fold reduced second-order rate con

37 Factor Va(3K), factor Va(K4/4A), and factor Va(6A) had r

38 ncubation with plasmin (4 nm) membrane-bound factor Va (400 nm) is completely inactive, whereas in th

39 n k cat, while prothrombinase assembled with factor Va(4A) exhibited an approximately 20% increase in

40 ating concentrations of factor Va(KF/4A) and factor Va(6A) had approximately 1.5-fold reduced second-

41 Factor Va(3K), factor Va(K4/4A), and factor Va(6A) had reduced affinity for factor Xa, when c

42 a crystal structure of protein C inactivated factor Va (A1.A3-C1-C2) that depicts a previously unchar

43 thrombinase assembled with factor Va (KF) or factor Va (AA) for prothrombin activation was approximat

44 studies showed that while factor Va (KF) and factor Va (AA) had a K D for factor Xa similar to the K

45 hrombinase assembled with factor Va (KF) and factor Va (AA) was reduced.

46 Maximum inhibition reduced the factor Va-accelerated rate to a level indistinguishable

47 The role of proexosite I in the mechanism of factor Va acceleration of prothrombin activation was inv

48 on between peptide binding and inhibition of factor Va acceleration.

49 tion in the absence of the protein cofactor, factor Va, allowed the direct observation of transient,

50 Factor Va, along with phospholipid and Ca2+, enhances th

51 little is known about the mechanism by which factor Va alters catalysis within this complex.

52 the last 13 residues from the heavy chain of factor Va (amino acid sequence 697-709, D13R) was found

53 inst PSP14 inhibited binding of protein S to Factor Va and blocked inhibition of prothrombinase activ

54 rately predicts the rates of inactivation of factor Va and factor VaLEIDEN, and the effect of product

55 ic inactivation of the coagulation cofactors factor Va and factor VIIIa.

56 Interactions between factor Va and membrane phosphatidylserine (PS) regulate

57 no acid region 307-351 of the heavy chain of factor Va and tested them for inhibition of prothrombina

58 gest that plasmin is a potent inactivator of factor Va and that region 307-348 of the cofactor plays

59 termediates may regulate their conversion to factor Va and that similar binding of thrombin to the fa

60 635 is essential for binding of protein S to Factor Va and that this interaction contributes to antic

61 at sphingosine disrupts interactions between factor Va and the Gla domain of factor Xa in the prothro

62 y inhibited the ability of APC to inactivate factor Va and to anticoagulate plasma.

63 rly Arg(165) and Lys(169), play key roles in factor Va and/or prothrombin recognition by FXa in proth

64 anticoagulant activities via inactivation of factors Va and VIIIa and cytoprotective activities via e

65 lotting cascade by inactivating procoagulant factors Va and VIIIa by limited proteolysis.

66 ctivity involves proteolytic inactivation of factors Va and VIIIa, and APC resistance is often caused

67 loops constitute interactive sites for both factors Va and VIIIa, thereby mediating the interaction

68 icoagulant activity involves inactivation of factors Va and VIIIa, whereas APC cytoprotective activit

69 ssive coagulation activation by inactivating factors Va and VIIIa.

70 late thrombin generation in vivo by cleaving factors Va and VIIIa.

71 gulates the coagulation cascade by degrading factors Va and VIIIa.

72 and the absence of control at the levels of factors Va and VIIIa.

73 of protein C and consequent inactivation of factors Va and VIIIa.

74 involve proteolysis of activated coagulation factors Va and VIIIa.

75 tic on the basis of inactivation of clotting factors Va and VIIIa; (2) a cytoprotective on the basis

76 rothrombinase, a Ca(2+)-dependent complex of factors Va and Xa assembled on the activated platelet su

77 apparent allosteric linkage between the S1, factor Va, and Na(+) sites to become evident and has pro

78 tide containing amino acid region 323-331 of factor Va (AP4') was found to be a potent inhibitor of p

79 onsequence binding of S1-directed probes and factor Va are adversely affected.

80 asmin demonstrated that while both chains of factor Va are cleaved by plasmin, only cleavage of the h

81 of APC inactivation of homocysteine-modified factor Va are consistent with the results of clotting as

82 that 10-fold higher concentrations of mutant factor Va are required for half-maximal prothrombinase a

83 time that cleavage of membrane-bound normal factor Va as well as membrane-bound factor V(LEIDEN) by

84 from the COOH terminus of the heavy chain of factor Va (Asp-Tyr-Asp-Tyr-Gln, DYDYQ) inhibits prothrom

85 onsists of the protease factor Xa, Ca2+, and factor Va assembled on an anionic membrane.

86 proteinase factor Xa and a cofactor protein, factor Va, assembled on membranes.

87 enhanced protein S-dependent APC cleavage in factor Va at Arg-506 by 13-fold, whereas PC/PS vesicles

88 Protein S enhances wild-type APC cleavage of factor Va at Arg306, but the inactivation rate of factor

89 basic C terminus and an acidic region in the factor Va B domain.

90 COOH-terminal portion of the heavy chain of factor Va, between amino acid residues 680 and 709.

91 duced interfacial packing does contribute to factor Va binding in the absence of PS, it does not corr

92 ontributes to the formation of the Na(+) and factor Va binding sites.

93 c peptides that have the potential to impair factor Va binding to any of the components of prothrombi

94 by directly mediating productive prothrombin-factor Va binding.

95 ggesting that PT-(1-46) inhibits prothrombin-factor Va binding.

96 on, but also significantly impairs Na(+) and factor Va binding.

97 Factor Va binds specifically to membrane-bound [OG488]-E

98 Factor V and factor Va bound to exosite I of [ANS]FPR-thrombin with s

99 inhibited by the peptides in the presence of factor Va but not in the absence of the cofactor.

100 icantly enhanced inactivation of coagulation factor Va by activated protein C (APC) and protein S, an

101 ffect of homocysteine on the inactivation of factor Va by activated protein C (APC) using clotting as

102 a may be related to impaired inactivation of factor Va by APC due to homocysteinylation of the cofact

103 Soluble EPCR inhibited the inactivation of factor Va by APC only in the presence of phospholipid ve

104 ies using purified proteins, inactivation of factor Va by APC:protein S was enhanced by GlcCer alone

105 g of the fragments deriving from cleavage of factor Va by plasmin demonstrated that while both chains

106 The mechanism of inactivation of bovine factor Va by plasmin was studied in the presence and abs

107 It is activated to factor Va by thrombin following proteolytic removal of a

108 Factor V, the precursor of factor Va, circulates in plasma with little or no procoa

109 ition above the membrane surface to optimize factor Va cleavage.

110 a (N42R) was found to be a good inhibitor of factor Va clotting activity with an IC(50) of approximat

111 ascertain the importance of this region for factor Va cofactor activity, we have synthesized eight o

112 ht chain formation and expression of optimum factor Va cofactor activity, whereas the latter two clea

113 a heavy chain are critical for expression of factor Va cofactor activity.

114 rothrombin as the substrate of the factor Xa-factor Va complex, possibly by directly mediating produc

115 prothrombin interactions with the factor Xa-factor Va complex.

116 ctional prothrombinase complex at saturating factor Va concentrations.

117 The heavy chain of factor Va contains an acidic region at the COOH terminus

118 boxyl-terminal portion of the heavy chain of factor Va contains hirudin-like motifs and appears to be

119 or prothrombin and the Kd(app) for factor Xa-factor Va decreased as a function of increasing PS conce

120 othrombin activation with recombinant mutant factor Va defective in factor Xa binding (E323F/Y324F an

121 Kinetics of factor Va degradation by APC mutants in purified systems

122 we found that prothrombinase assembled with factor Va(Delta680-709) displayed an approximately 39% i

123 catalyzed the activation of prothrombin in a factor Va-dependent manner and exhibited identical activ

124 residues of proexosite-1 on prothrombin are factor Va-dependent recognition sites for factor Xa in t

125 ously demonstrated role of (pro)exosite I in factor Va-dependent substrate recognition suggest that c

126 )exosite I and the role of (pro)exosite I in factor Va-dependent substrate recognition suggest that t

127 Factor Va derived from homocysteine-treated factor V was

128 Factor Va, derived from factor V treated with 1 mm beta-

129 Factor Xa and factor Va did not bind the peptide with significant affi

130 Factor Va directs prothrombin activation by factor Xa th

131 Thrombin-activated factor Va exists as two isoforms, factor Va(1) and facto

132 Xa similar to the K D observed for wild-type factor Va (factor Va (WT)), the clotting activities of t

133 mpared to the clotting activity of wild-type factor Va (factor Va (Wt)).

134 Thrombin activated factor Va (factor VIIa, residues 1-709 and 1546-2196) ha

135 Thus, the peptide interferes with the factor Va-factor Xa interaction.

136 f factor Xa, indicating stabilization of the factor Va-factor Xa-membrane complex.

137 e (factor VIIIa/factor IXa), prothrombinase (factor Va/factor Xa), and factor XIa complexes on PS-exp

138 y be involved in prothrombinase complex (fXa.factor Va.fII.phospholipids) assembly, synthetic peptide

139 this oligosaccharide reduces the affinity of factor Va for biological membranes.

140 We found that the affinity of mutant factor Va for membranes containing 25% PS was reduced at

141 ot appear to be a significant contributor to factor Va formation.

142 consistent with the following mechanism for factor Va formation.

143 KIn-I, together with heparin, also protected factor Va from APC-mediated inactivation.

144 dominant role in the binding of factor V and factor Va from the effect of the exosite I-specific liga

145 Factor Va functions both as a receptor for factor Xa and

146 f prothrombin in the presence and absence of factor Va (FVa) and 5.0 x 10(-5) M phospholipid vesicles

147 anticoagulant pathway, where it enhances the factor Va (FVa) and factor VIIIa (FVIIIa) inactivating p

148 ic inactivation of the coagulation cofactors factor Va (FVa) and factor VIIIa.

149 Generation of active procoagulant cofactor factor Va (FVa) and its subsequent association with the

150 Removal of the B domain and generation of factor Va (fVa) are vital for procoagulant activity.

151 Activated protein C (APC) cleavage of Factor Va (FVa) at residues R506 and R306 correlates wit

152 peptide sequence reported to interfere with factor Va (FVa) binding.

153 Activated protein C (APC) inactivates factor Va (fVa) by proteolytically cleaving fVa heavy ch

154 xpressed on factor V (FV) upon activation to factor Va (FVa) by thrombin.

155 ependent interaction of factor Xa (FXa) with factor Va (FVa) forms prothrombinase and drives thrombin

156 e phenomena occurred with increased rates of factor Va (fVa) inactivation by cleavages at R(506) and

157 Interestingly, factor Va (fVa) restored most of the catalytic defect wi

158 Platelet- and plasma-derived factor Va (FVa) serve essential cofactor roles in prothr

159 Activated fXR347N had a reduced affinity for factor Va (fVa), although the catalytic impact of fVa bi

160 , factor Xa (fXa), and a regulatory subunit, factor Va (fVa), assembled on a membrane surface in the

161 Prothrombinase inhibition by PT473-487 was factor Va (fVa)-dependent and sequence-specific, because

162 e to APC caused by decreased inactivation of factor Va (FVa).

163 fXa) contributes to binding of the cofactor, factor Va (fVa).

164 otein C (APC), inactivates blood coagulation factors Va (FVa) and VIIIa.

165 and 102-116 in factor Xa (fXa) may harbor a factor Va- (fVa-) dependent prothrombin recognition site

166 The variants require factor Va generated in situ for procoagulant function, a

167 40 +/- 280 pM for factor XIII activation and factor Va generation (2.2 +/- 0.6 minutes), 1.3 +/- 0.4

168 , platelet activation (osteonectin release), factor Va generation, fibrinopeptide (FP) A and FPB rele

169 e, a systematic definition of the regions of factor Va governing its incorporation within prothrombin

170 ntly shown that amino acid region 307-348 of factor Va heavy chain (42 amino acids, N42R) is critical

171 monstrated that amino acid region 323-331 of factor Va heavy chain (9 amino acids, AP4') contains a b

172 del for the carboxyl-terminal peptide of the factor Va heavy chain (Ser(664)-Arg(709)) and incorporat

173 sidues Glu323, Tyr324, Glu330, and Val331 of factor Va heavy chain are critical for expression of fac

174 together with amino acid region 695-698 from factor Va heavy chain are part of a cooperative mechanis

175 323), Y (324), E (330), and V (331) from the factor Va heavy chain are required for the interaction o

176 onstrate that amino acid sequence 323-331 of factor Va heavy chain contains a binding site for factor

177 rst time that amino acid sequence 695-698 of factor Va heavy chain is important for procofactor activ

178 demonstrate that the COOH-terminal region of factor Va heavy chain is indeed crucial for coordinated

179 bution of the acidic COOH-terminal region of factor Va heavy chain to factor Xa activity within proth

180 In similar mixtures containing factor Va, however, PZ and ZPI do not inhibit thrombin g

181 activated protein C (APC) inactivated bovine factor Va(i) (without the A2 domain) suggests a complete

182 sults from its activation by alpha-thrombin, factor Va(IIa) (FVa(IIa)).

183 nitial activation of factor V; generation of factor Va in a milieu already containing factor Xa enabl

184 cleavage, depending on the incorporation of factor Va in prothrombinase.

185 n of Gla-domainless prothrombin by factor Xa/factor Va in the absence of phospholipids (IC(50) = 0.49

186 oducts, a model is developed which describes factor Va inactivation and accounts for the defect in fa

187 In factor Va inactivation assays, protein S E36A had 89% re

188 Both cations were required for efficient factor Va inactivation by aGDPC.

189 e isolated immunoglobulin fraction inhibited factor Va inactivation by APC because of impaired cleava

190 brane surface, as prothrombin also inhibited factor Va inactivation by APC in the absence of a membra

191 odel in order to understand the mechanism of factor Va inactivation by APC.

192 atidylcholine (PC) dose dependently enhanced factor Va inactivation by the anticoagulant factors, act

193 s more inhibitory to both prothrombinase and factor Va inactivation in the presence of PE.

194 (PE) and phosphatidylcholine (PC) supported factor Va inactivation relatively well.

195 However, optimal factor Va inactivation still required relatively high co

196 Thus, PE makes an important contribution to factor Va inactivation that cannot be mimicked by PS.

197 systems, anti-beta(2)-GPI mAb inhibition of factor Va inactivation was greater in the presence of pr

198 ability of protein S to enhance APC-mediated factor Va inactivation.

199 Compared with normal factor Va, inactivation of factor Va Leiden by APC was m

200 rane-bound factor Xa alone in the absence of factor Va increasing the rate for cleavage at Arg(271) o

201 ce, providing direct evidence of a PT-(1-46)-factor Va interaction.

202 Factor Va interactions of human and bovine prothrombin a

203 These results suggest that factor Va interacts with 185-189-loop for fXa, which is

204 Thus, modulation of the incorporation of factor Va into prothrombinase in vivo by using synthetic

205 bin, incorporation of the cofactor molecule, factor Va, into prothrombinase results in a five orders

206 e catalytic sequence leading to formation of factor Va is a subject of disagreement.

207 whether occupancy of this PS binding site in factor Va is also required for high-affinity binding to

208 activation of the procofactor, factor V, to factor Va is an essential reaction that occurs early in

209 Finally, the membrane-binding site of factor Va is contributed by several elements of the ligh

210 at Arg(271) and suggest that this portion of factor Va is partially responsible for the enhanced proc

211 However, factor Va is prone to inactivation by activated protein

212 Factor Va is the critical cofactor for prothrombinase as

213 al. proposed an incomplete homology model of factor Va (it lacks 46 amino acids from the carboxyl ter

214 pared in assays containing phospholipids and factor Va, K1K2C and TFPI-160 are poor inhibitors compar

215 Factor Va(3K), factor Va(K4/4A), and factor Va(6A) had reduced affinity

216 Kinetic studies showed that while factor Va (KF) and factor Va (AA) had a K D for factor X

217 d the k cat of prothrombinase assembled with factor Va (KF) and factor Va (AA) was reduced.

218 te constant of prothrombinase assembled with factor Va (KF) or factor Va (AA) for prothrombin activat

219 assembled with saturating concentrations of factor Va(KF/4A) and factor Va(6A) had approximately 1.5

220 The absence or dysfunction of factor Va leads to hemorrhagic diseases while prolonged

221 pared with normal factor Va, inactivation of factor Va Leiden by APC was much less sensitive to proth

222 r Va at Arg306, but the inactivation rate of factor Va Leiden by the chimera alone is essentially equ

223 The APC binding site resides in the factor Va light chain (LC) (Kd = 7 nM), suggesting that

224 p(2064), have been proposed to contribute to factor Va membrane interactions by insertion into the hy

225 e of high NaCl or with saturating amounts of factor Va membranes, suggesting that allosteric linkage

226 gions encoding the APC cleavage sites in the factor Va molecule excluded the presence of the factor V

227 ng established, the peptidyl portions of the factor Va molecule responsible for its interactions with

228 edge with respect to the interactions of the factor Va molecule with the various components of prothr

229 containing the NH(2)-terminal portion of the factor Va molecule.

230 Two mutant recombinant factor Va molecules (Glu323 --> Phe/Tyr324 --> Phe, fact

231 on cofactor activity, we created recombinant factor Va molecules combining mutations at amino acid re

232 otting activities of both recombinant mutant factor Va molecules were impaired compared to the clotti

233 ide encompassing the region 307-348 of human factor Va (N42R) was found to be a good inhibitor of fac

234 of factor Xa in the prothrombinase complex (factor Va, negatively charged membrane surfaces, and cal

235 The interaction of factor Xa with factor Va on membranes to form prothrombinase profoundly

236 posed of the proteinase, factor Xa, bound to factor Va on membranes, catalyzes thrombin formation by

237 had anticoagulant activity in the absence of factor Va or phospholipids.

238 2R encompassing amino acid region 337-351 of factor Va (P15H) had no effect on either prothrombinase

239 g constants, and product activity values for factor Va partial inactivation products, a model is deve

240 y of this natural anticoagulant by rendering factor Va partially resistant to inactivation by activat

241 P3-P3' residues of the APC cleavage site in factor Va, particularly P2Arg, confer specificity for th

242 Xa in the prothrombinase complex (factor Xa, factor Va, phosphatidylcholine/phosphatidylserine vesicl

243 athway used was independent of the source of factor Va (plasma- or platelet-derived) and was unaffect

244 and that similar binding of thrombin to the factor Va produced may reflect a mode of interaction inv

245 binding to anionic phospholipid vesicles and factor Va proteolysis in the presence and absence of pro

246 eaction mixtures composed only of factor Xa, factor Va, prothrombin, and calcium ions, myosin greatly

247 pid vesicles of the membrane-bound factor Xa-factor-Va-prothrombin complex.

248 Because factor V and factor Va receptors are found on vascular endothelium an

249 t mutations in the factor Xa binding site of factor Va reduce rates for both bonds.

250 Factor Va reduced by 100-fold the apparent Kd of myosin

251 from the COOH terminus of the heavy chain of factor Va regulates the rate of cleavage of prothrombin

252 Plasma and platelet factor Va represent different substrates for activated p

253 Interestingly, a saturating concentration of factor Va restored the catalytic defect of K186A in reac

254 ndicating that the conversion of factor V to factor Va results in appropriate structural changes, whi

255 Factor Va(RVV)(2K2F) and factor Va(Xa)(2K2F) had impaire

256 uld be readily activated by RVV-V activator (factor Va(RVV)(2K2F)) and factor Xa (factor Va(Xa)(2K2F)

257 the apparent allosteric linkage between the factor Va, S1, and Na(+)-binding sites, since binding of

258 In vertebrate hemostasis, factor Va serves as the cofactor in the prothrombinase c

259 largest physiologically relevant fragment of factor Va solved to date and provides a new scaffold for

260 raction of factor Xa with the heavy chain of factor Va strongly influences the catalytic activity of

261 factor Xa in the presence but not absence of factor Va, suggesting that PT-(1-46) inhibits prothrombi

262 sed of an enzyme, factor Xa, and a cofactor, factor Va, that each bind peripherally to membranes cont

263 Factor Va, the cofactor of prothrombinase, is composed o

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

265 proteinase, thrombin, converts factor V into factor Va through a multistep activation pathway that is

266 The binding of mutant factor Va to 25% PS membranes was markedly enhanced in t

267 were unable to interfere with the binding of factor Va to active site fluorescently labeled Glu-Gly-A

268 L) and FXa(V17A) on activated platelets with factor Va to form prothrombinase completely restores bio

269 The ability of the mutant factor Va to interact with factor Xa on a membrane was a

270 tested for the inhibition of the binding of factor Va to membrane-bound active site fluorescent labe

271 ritical role in the high-affinity binding of factor Va to PS membranes.

272 The addition of factor Va to PT-(1-46) labeled with the fluorophore sulf

273 an essential and productive contribution of factor Va to the activity of prothrombinase.

274 t anticoagulant serine protease, inactivates factors Va/VIIIa.

275 rts anticoagulant activity by proteolysis of factors Va/VIIIa.

276 of Arg(74) and Arg(75) mutants to inactivate factor Va was markedly impaired.

277 Factor Va was required for the anticoagulant property of

278 Factor Va was treated with plasmin in the absence of pho

279 Affinity of the mutant for binding to factor Va was weakened and its ability to activate proth

280 r complex formation and cleavage to generate factor Va, was investigated using a site-directed mutage

281 Using our completed model of human factor Va, we are also demonstrating for the first time

282 urating concentrations of recombinant mutant factor Va were calculated, prothrombin activation was as

283 The interaction of factor Va with 25% PS membranes was also characterized u

284 napeptide inhibits the direct interaction of factor Va with [OG488]-EGR-hXa (IC50 approximately 7.5 m

285 e other hand, the FXa mutant interacted with factor Va with a normal apparent dissociation constant a

286 rombinase complex revealed that FXa binds to factor Va with a similar K(d(app)) of 1.1-1.8 nM in the

287 oline and phosphatidylethanolamine (PE) bind factor Va with high affinity (K(d) = approximately 10 nm

288 We show that all mutants interacted with factor Va with normal affinities and exhibited wild-type

289 ars to be responsible for the interaction of factor Va with prothrombin.

290 plicated in providing a recognition site for factor Va within prothrombinase.

291 to the K D observed for wild-type factor Va (factor Va (WT)), the clotting activities of the mutant m

292 he clotting activity of wild-type factor Va (factor Va (Wt)).

293 obtained with prothrombinase assembled with factor Va (WT).

294 n catalyzed by prothrombinase assembled with factor Va (WT).

295 d to the affinity of the wild-type molecule (factor Va(Wt)) for the enzyme.

296 obtained with prothrombinase assembled with factor Va(Wt), while prothrombinase assembled with satur

297 uced clotting activities compared to that of factor Va(WT).

298 ecules for factor Xa was similar to that for factor Va(WT).

299 as compared to prothrombinase assembled with factor Va(Wt).

300 Factor Va(RVV)(2K2F) and factor Va(Xa)(2K2F) had impaired cofactor activity withi

301 ivator (factor Va(RVV)(2K2F)) and factor Xa (factor Va(Xa)(2K2F)).