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 in the production of autoantibodies against FXIIIa in acquired FXIII deficiency, TG2 in celiac disea

9 Although FXIIIa co-localizes with Abeta in CAA, the ability of FX

10 An FXIIIa-sensitive near-infrared fluorescence imaging agen

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

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

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

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

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

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

17 6R, gamma-dimer cross-links were absent, but FXIIIa produced a cross-linking pattern similar to that

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

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

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

21 verine in comparison to residues modified by FXIIIa.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

37 2+), the integrin alphaIIbbeta3, myosin IIa, FXIIIa cross-linking, and platelet count all promote 1 o

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

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

40 Moreover, FXIIIa inhibitor concentrations that primarily block alp

41 -localizes with Abeta in CAA, the ability of FXIIIa to cross-link Abeta has not been demonstrated.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

58 atively small number of individuals: loss of FXIIIa (transamidase-activated form) crosslinking leads

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

60 latelet-rich plasma clots in the presence of FXIIIa.

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

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

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

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

65 esentative displaying inhibitory activity on FXIIIa.

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

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

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

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

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

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

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

73 XIIIa allostery and the presence of putative FXIIIa exosites.

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

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

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

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

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

79 ays, and microfluidic analyses, we show that FXIIIa covalently cross-links Abeta40 into dimers and ol

80 These results suggest that FXIIIa-mediated cross-linking may contribute to the form

81 The FXIIIa inhibitors K9 DON and iodoacetamide both promoted

82 The FXIIIa inhibitory activity of the analogues was retained

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

99 es as well as molecular docking studies with FXIIIa were performed to elucidate the impact of the C(1

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

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

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

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

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

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

106 and activated blood coagulation factor XIII (FXIIIa).

107 the activated transglutaminase factor XIII (FXIIIa).

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

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

110 Activated coagulation factor XIIIa (FXIIIa) covalently cross-links proteins in blood and vas

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

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

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

114 erization and cross-linking by factor XIIIa (FXIIIa).