ライフサイエンスコーパス: FXIIIa

1 FXIIIa additionally cross-links several proteins with ot

2 FXIIIa also mediates red blood cell (RBC) retention in c

3 FXIIIa cross-links alpha(2)AP and an alpha(2)AP peptide,

4 FXIIIa inhibition reduced RBC retention in clots formed

5 The results revealed a total of 147 FXIIIa substrates, of which 132 have not previously been

6 e polymerization of fibrin monomers, and (4) FXIIIa-catalyzed cross-link formation.

7 of a suitable lead structure for addressing FXIIIa.

8 An FXIIIa-sensitive near-infrared fluorescence imaging agen

9 he most pertinent TG isoforms (TG1, TG3, and FXIIIa).

10 e and mutant forms of alpha2AP functioned as FXIIIa substrates with affinities and kinetic efficienci

11 tions of FXIII by IIa and by Ca2+ as well as FXIIIa inhibition by the K9 DON peptide (with the Q isos

12 ), and pentylamine into fibrin by clot-bound FXIIIa declined rapidly with half-lives of 19, 21, and 2

13 In vivo, the ability of thrombus-bound FXIIIa to cross-link an infused alpha(2)AP(13-24) peptid

14 bstrate positions are sensitive to the broad FXIIIa substrate specificity pockets.

15 6R, gamma-dimer cross-links were absent, but FXIIIa produced a cross-linking pattern similar to that

16 n(447), but became cross-linked to fibrin by FXIIIa or tTG at approximately one-tenth the rate for WT

17 hat is specifically crosslinked to fibrin by FXIIIa, permitting detection of FXIIIa activity in exper

18 ed that Q237 is rapidly crosslinked first by FXIIIa followed by Q366 and Q328.

19 verine in comparison to residues modified by FXIIIa.

20 s labeled with 5-(biotinamido)pentylamine by FXIIIa or tTG catalysis.

21 (-) DC, CD1a(-)CD14(+) DC, and CD1a(-)CD14(+)FXIIIa(+) macrophages.

22 Here, we show that plasmin can cleave FXIIIa in purified systems and in blood.

23 iscrete populations of CD11c(+) myeloid DCs, FXIIIa(+) Mphi, and lymphocytes.

24 ied, the characteristic features that define FXIIIa substrate specificity are not well understood.

25 Both plasma- and platelet-derived FXIIIa were susceptible to plasmin-mediated degradation.

26 ot formation and consolidation and establish FXIIIa activity as a key determinant of thrombus composi

27 valuate the molecular specificity of A15 for FXIIIa, a control agent (C15) was also synthesized by mo

28 lysis by competing with native alpha2AP for FXIIIa-catalyzed incorporation into fibrin.

29 alphaC (233-425) contains a binding site for FXIIIa and three glutamines Q237, Q328, and Q366 that ea

30 ow that alpha(2)AP is a better substrate for FXIIIa than for this particular tTG, but that either enz

31 Active FXIII (FXIIIa) catalyzes the formation of epsilon-(gamma-glutam

32 To learn more about how FXIIIa selects its targets, a matrix-assisted laser deso

33 elated with fibrin network density; however, FXIIIa inhibition reduced RBC retention at all network d

34 ansglutaminase-specific labeling to identify FXIIIa plasma protein substrates and their reactive resi

35 2+), the integrin alphaIIbbeta3, myosin IIa, FXIIIa cross-linking, and platelet count all promote 1 o

36 The time-related changes in FXIIIa activity in clots was measured with (1) alpha(2)-

37 These data indicate FXIIIa-dependent retention of RBCs in clots is mediated

38 Moreover, FXIIIa inhibitor concentrations that primarily block alp

39 RBC loss from clots formed in the absence of FXIIIa activity, and RBCs exhibited transient deformatio

40 corporation showed the k(cat)/K(m)((app)) of FXIIIa to be 3-fold greater than that of tTG for WT-alph

41 Kinetic efficiencies (k(cat)/K(m)((app))) of FXIIIa and the guinea pig liver tissue transglutaminase

42 This agent should permit assessment of FXIIIa activity in a broad range of biological processes

43 To study the contribution of FXIIIa-induced gamma-chain cross-linking on fibrin struc

44 urs), consistent with an expected decline of FXIIIa activity over time.

45 to fibrin by FXIIIa, permitting detection of FXIIIa activity in experimental thrombi in vivo.

46 e active site of TG2 and terminal domains of FXIIIa.

47 he antifibrinolytic cross-linking effects of FXIIIa are achieved more rapidly in thrombi than previou

48 ional insight into the potential function of FXIIIa-positive dermal dendrocytes in skin remodeling an

49 In vivo imaging of FXIIIa activity could further elucidate the role of this

50 o describe the physiological inactivation of FXIIIa has been elusive.

51 Inactivation of FXIIIa occurred during clot lysis and was enhanced both

52 ctive-center-directed synthetic inhibitor of FXIIIa, 1,3-dimethyl-4,5-diphenyl-2[2(oxopropyl)thio]imi

53 d by a synthetic, active-center inhibitor of FXIIIa.

54 ps either lacked or possessed a low level of FXIIIa substrate activity.

55 III (FXIIIa), we examined the persistence of FXIIIa catalytic activity in clots of various ages.

56 t turbidity, clot structure, and the rate of FXIIIa cross-linking.

57 The results of FXIIIa-catalyzed incorporation of dansylcadaverine and d

58 to be highly specific for the active site of FXIIIa and was covalently bound to fibrin.

59 se three glutamines and probe for sources of FXIIIa substrate specificity.

60 esentative displaying inhibitory activity on FXIIIa.

61 New knowledge on FXIIIa specificity may be used to design better substrat

62 Important glimpses are being provided on FXIIIa allostery and the presence of putative FXIIIa exo

63 try did not reveal crosslinking of fibrin or FXIIIa substrates to RBCs, suggesting FXIIIa does not cr

64 mino-terminus affected plasmin-inhibitory or FXIIIa substrate activities of wild-type alpha2AP.

65 is believed to be a fibrin-cross-linking (or FXIIIa-reactive) site.

66 ted FN constructs revealed efficient TG2- or FXIIIa-catalyzed dansylcadaverine incorporation into the

67 en FXIII was not readily cleaved by plasmin, FXIIIa was rapidly cleaved and inactivated by plasmin in

68 XIIIa allostery and the presence of putative FXIIIa exosites.

69 rin or FXIIIa substrates to RBCs, suggesting FXIIIa does not crosslink RBCs directly to the clot.

70 Thus, these results demonstrate that FXIIIa and TG2 act similarly on glutamines at either end

71 These results indicate that FXIIIa activity can be modulated by fibrinolytic enzymes

72 This indicates that FXIIIa activity is a hallmark of new thrombi and that th

73 veral known substrate proteins revealed that FXIIIa displays a preference for the glutamine residue i

74 The FXIIIa inhibitors K9 DON and iodoacetamide both promoted

75 morphology is only minimally altered by the FXIIIa-catalyzed cross-linking reaction, which seems to

76 When it was tested in the FXIIIa-mediated fibrin cross-linking reaction, the 1Q Fn

77 in monomers persisted in the presence of the FXIIIa inhibitor K9-DON, illustrating that cross-linking

78 We confirm that 48 of the FXIIIa substrates were indeed incorporated into the inso

79 Results suggest that the FXIIIa active site surface responds to changes in substr

80 Our findings indicate that the FXIIIa-induced dimeric cross-linking of gamma-chains by

81 ating RBC retention does not depend on these FXIIIa substrates.

82 This FXIIIa kinetic assay is no longer reliant on a secondary

83 isomer preference with respect to binding to FXIIIa, in turn, the knowledge of the enzyme-inhibitor i

84 he loss of activity was not due primarily to FXIIIa proteolysis and was partially restored by reducin

85 iously identified, their reactivities toward FXIIIa have not been ranked.

86 n assists in activating the transglutaminase FXIIIa that incorporates cross-links into the fibrin clo

87 However, the mechanism by which FXIIIa retains RBCs in clots is unknown.

88 With FXIIIa or tTG catalysis, [(14)C]methylamine was incorpor

89 ins of greater clot rigidity associated with FXIIIa-dependent cross-linking.

90 We observed that ligation with FXIIIa nearly doubled the stiffness of the fibers.

91 n when activated blood clotting factor XIII (FXIIIa) catalyzes the formation of an isopeptide bond be

92 Activated factor XIII (FXIIIa) catalyzes the formation of gamma-glutamyl-epsilo

93 sglutaminase reaction activated factor XIII (FXIIIa) covalently cross-links von Willebrand factor (VW

94 Activated coagulation factor XIII (FXIIIa) cross-links the gamma-chains of fibrin early in

95 Activated factor XIII (FXIIIa) mediates fibrinolytic resistance and is a hallma

96 ction of fibrin-bound activated factor XIII (FXIIIa), we examined the persistence of FXIIIa catalytic

97 and activated blood coagulation factor XIII (FXIIIa).

98 the activated transglutaminase factor XIII (FXIIIa).

99 taminase, also termed activated factor XIII (FXIIIa).

100 step in blood coagulation, the factor XIIIa (FXIIIa) catalyzed cross-linking of fibrin monomers, is c

101 Factor XIIIa (FXIIIa) introduces covalent gamma-glutamyl-epsilon-lysyl

102 Coagulation factor XIIIa (FXIIIa) is a transglutaminase that covalently cross-link

103 od cells (RBCs), fibrin(ogen), factor XIIIa (FXIIIa), and thrombin on the kinetics and mechanics of t