ライフサイエンスコーパス: prethrombin

1 Cleavage at Arg320 of ProT or prethrombin 1 (Pre 1) activates the catalytic site and t

2 distinguished exosite I environments on Pro, prethrombin 1 (Pre 1), and prethrombin 2 (Pre 2) but bou

3 FPR-prethrombin 1 (Pre 1), fragment 1 (F1), fragment 1.2 (F1

4 fragment 1 and generates the zymogen analog, prethrombin 1 (Pre 1).

5 active products of factor Xa-catalyzed human prethrombin 1 activation in the absence of the protein c

6 present, these differences in protein C and prethrombin 1 activation rates were decreased to about 2

7 Loss of fragment 1 in prethrombin 1 enhanced affinity for both vWbp(1-263) and

8 ntrinsic property of factor Xa activation of prethrombin 1 that is modulated by factor Va.

9 brium binding to the prothrombin derivatives prethrombin 1, prethrombin 2, thrombin, meizothrombin, a

10 et mutants of des-(1-45)-factor Xa activated prethrombin 1.8-11-fold slower than wild-type enzyme.

11 activation of the charge reversal mutants of prethrombin-1 (in particular K36E, R67E, and K70E) were

12 n this study, we prepared several mutants of prethrombin-1 (prothrombin lacking Gla and Kringle-1 dom

13 y, the activation of proexosite-1 mutants of prethrombin-1 by the partially purified venom was studie

14 Prethrombin-1 differs from prothrombin for the absence o

15 The X-ray crystal structure of prethrombin-1 solved at 2.2-A resolution shows an overal

16 minutes), 1.7 +/- 0.5 nM for FPB release and prethrombin 2 (2.8 +/- 0.8 minutes), 7.0 +/- 2.2 nM for

17 he membrane binding domain is also lost when prethrombin 2 (P2) and F12 are produced following initia

18 ironments on Pro, prethrombin 1 (Pre 1), and prethrombin 2 (Pre 2) but bound with the same affinities

19 Prethrombin 2 (Pre 2), formed by factor Xa cleavage of P

20 om meizothrombin toward formation of the FPR-prethrombin 2 (Pre 2).F1.2 inhibitory intermediate.

21 g271 produces the inactive zymogen form, the prethrombin 2 (Pre 2).fragment 1.2 complex, which is cle

22 ombin, was a linear competitive inhibitor of prethrombin 2 activation without significantly inhibitin

23 24 mumol/L) is consumed yielding 400 nmol/ L prethrombin 2 and 360 nmol/l thrombin (B-chain) products

24 Prethrombin 2 and alpha-thrombin compete for binding to

25 be accounted for by a kinetic model in which prethrombin 2 and alphaBFX-2b bind in a mutually exclusi

26 interacts with the 148 loop of thrombin and prethrombin 2 and the south rim of the catalytic site, w

27 We have used prethrombin 2 as a substrate analog for the first cleava

28 By kinetic studies of prethrombin 2 cleavage by prothrombinase in the presence

29 The kcat/Km for prethrombin 2 cleavage by prothrombinase was essentially

30 city measurements indicated that the rate of prethrombin 2 cleavage by the factor Xa-PCPS binary comp

31 We show that competitive inhibition of prethrombin 2 cleavage can be accomplished by interferin

32 The kinetics of prethrombin 2 cleavage was studied to delineate macromol

33 n following initial cleavage at Arg(271) and prethrombin 2 formation (pre2 pathway).

34 binding inhibitor of the cleavage of either prethrombin 2 or meizothrombin des-fragment 1 by prothro

35 ge of phospholipid-bound prothrombin via the prethrombin 2 pathway, catalyzes the initial activation

36 e intermediates, meizothrombin (MzII(a)) and prethrombin 2 plus fragment 1.2 (Pre2 & F1.2).

37 rombin 2, prethrombin 2 plus fragment 2, and prethrombin 2 plus fragment 1.2 as substrates.

38 constants were obtained using prethrombin 2, prethrombin 2 plus fragment 2, and prethrombin 2 plus fr

39 s essentially identical to that obtained for prethrombin 2 saturated with fragment 2.

40 g residues 1-325 (SC-(1-325)) bound to human prethrombin 2 showed previously that SC inserts its Ile(

41 and have also relied on the known ability of prethrombin 2 to interact tightly but reversibly with fr

42 Both alpha-thrombin and prethrombin 2 were cleaved with chymotrypsin at Trp148 a

43 Val(2) N terminus into the Ile(16) pocket of prethrombin 2, inducing a functional active site in the

44 ive site-independent binding of prothrombin, prethrombin 2, meizothrombin des fragment 1 and thrombin

45 state kinetic constants were obtained using prethrombin 2, prethrombin 2 plus fragment 2, and prethr

46 o the prothrombin derivatives prethrombin 1, prethrombin 2, thrombin, meizothrombin, and meizothrombi

47 Binding was inferred by prethrombin 2-dependent perturbations in the fluorescenc

48 ile hydrolysis of Arg(273)-Thr(274) produces prethrombin 2-fragment 1.2 (Pre2-F1.2).

49 l substrates does not alter the affinity for prethrombin 2.

50 nesis of the authentic P(1)-P(3) sequence in prethrombin 2/fragment 1.2 yielded substrate variants th

51 ase takes place without preference along the prethrombin-2 (cleavage at Arg(271) first) or meizothrom

52 t Arg-271, generating the inactive precursor prethrombin-2 (Pre2), which is further attacked at Arg-3

53 CPS markedly accelerated the initial rate of prethrombin-2 activation by E2-fXa, with the cofactor ex

54 nition by thrombin and its zymogen precursor prethrombin-2 and have direct relevance to other members

55 Crystal structures of both prethrombin-2 and thrombin are available and show almost

56 to glucokinase, thrombin, and its precursor prethrombin-2 are used as relevant examples.

57 protease thrombin and its zymogen precursor prethrombin-2 as relevant models we resolve the relative

58 inhibitors of the fVa-mediated activation of prethrombin-2 by E2-fXa in the absence of PCPS, they are

59 Since neither E2-fXa nor prethrombin-2 can interact with membranes, these results

60 Prothrombin and prethrombin-2 gave nearly identical results while meizot

61 The thrombin precursor prethrombin-2 has R15 at the site of activation in ionic

62 of E* and E forms observed for thrombin and prethrombin-2 indicates that zymogen activation is linke

63 -320, leading to thrombin generation via the prethrombin-2 intermediate.

64 Addition of mutated mouse prethrombin-2 into the conventional assay for prothrombi

65 We hypothesize that use of the prethrombin-2 pathway serves to optimize the procoagulan

66 In the blood, the zymogens prothrombin and prethrombin-2 require the prothrombinase complex to be c

67 e pairs of chymotrypsinogen, trypsinogen and prethrombin-2 showed a similar distribution of the flexi

68 to proceed through the inactive intermediate prethrombin-2 via an initial cleavage at Arg-271 followe

69 mediated catalytic activity of E2-fXa toward prethrombin-2 was analyzed in both the absence and prese

70 duced recombinant mutants of human and mouse prethrombin-2 which are able to convert themselves autoc

71 mutant was expressed in Escherichia coli as prethrombin-2(148) using a T7 expression system previous

72 After refolding and purification, prethrombin-2(148) was activated to thrombin(148) with E

73 a and both kringle domains of the substrate (prethrombin-2) had been deleted.

74 rombin with the same regions of prothrombin, prethrombin-2, and meizothrombin.

75 t Arg271 generates the inactive intermediate prethrombin-2, initial cleavage at Arg320 generates the

76 In the case of prethrombin-2, the equilibrium is shifted strongly (10:1

77 her potential intermediate, meizothrombin or prethrombin-2, was observed in the effluent.

78 gh prothrombin is much larger than thrombin, prethrombin-2, which contains all of the same amino acid

79 n was initially cleaved at Arg271 generating prethrombin-2, with alpha-thrombin formation quickly aft

80 d through the intermediates meizothrombin or prethrombin-2.

81 the same positions as E14e, D14l, and E18 in prethrombin-2.

82 teases: chymotrypsinogen, proproteinase, and prethrombin-2.

83 on system previously described for wild-type prethrombin-2.

84 , which is unable to activate prothrombin or prethrombin-2.

85 Both AN78 and AN129 bound to prethrombin I (the fragment lacking the Gla domain and t

86 lel pathways: (1) the inactive intermediate, prethrombin; or (2) the proteolytically active intermedi