Dissociation of the subunit structure of fibrin stabilizing factor during activation of the zymogen

Lóránd, L.; Gray, A.; Brown, Koshonna; Credo, R.B.; Curtis, C. G.; Domanik, R.A.; Stenberg, P.

doi:10.1016/s0006-291x(74)80275-5

Cited by 99 publications

(46 citation statements)

References 16 publications

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“…This lag phase in activation represents the time it takes for the B-subunits to dissociate from plasma factor XIIIa. 25,27,28 Dissociation of the Bfrom the A-subunits is necessary to expose the active-site cysteine in plasma factor XIII A-subunit ( Figure 2). There are no B-subunits bound to the fibrin clot, suggesting that B dissociates as fibrin gels.…”

Section: Factor XIII Activationmentioning

confidence: 99%

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms

Ariëns

Lai

Weisel

et al. 2002

Blood

329

272

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Factor XIII and fibrinogen are unusual among clotting factors in that neither is a serine protease. Fibrin is the main protein constituent of the blood clot, which is stabilized by factor XIIIa through an amide or isopeptide bond that ligates adjacent fibrin monomers. Many of the structural and functional features of factor XIII and fibrin(ogen) have been elucidated by protein and gene analysis, site-directed mutagenesis, and x-ray crystallography. However, some of the molecular aspects involved in the complex processes of insoluble fibrin formation in vivo and in vitro remain unresolved. The findings of a relationship between fibrinogen, factor XIII, and cardiovascular or other thrombotic disorders have focused much attention on these 2 proteins. Of particular interest are associations between common variations in the genes of factor XIII and altered risk profiles for thrombosis. Although there is much debate regarding these observations, the implications for our understanding of clot formation and therapeutic intervention may be of major importance. In this review, we have summarized recent findings on the structure and function of factor XIII. This is followed by a review of the effects of genetic polymorphisms on protein structure/function and their relationship to disease. (Blood. 2002;100:743-754)

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Section: Factor XIII Activationmentioning

confidence: 99%

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms

Ariëns

Lai

Weisel

et al. 2002

Blood

329

272

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“…The B subunits also contribute to binding the zymogen to fibrinogen 50 and act as a brake on factor XIII activation. 51 Thrombin and Ca 2ϩ are required for conversion into the active factor XIIIa enzyme, 52-55 but the thrombin-catalyzed cleav- age near the N-termini of the A subunits only weakens the heterologous association of the subunits 56 and still leaves the zymogen in an inert tetrameric (A 2 ЈB 2 ) form (Figure 4). Expression of enzyme activity depends on the Ca 2ϩ -facilitated dissociation of A 2 Ј from the carrier B 2 subunits and on a concerted conformational change that unmasks the hidden sulfhydryl catalytic centers for the A 2 * (FXIII a ) cross-linking enzyme.…”

Section: The Urea-insoluble Clotmentioning

confidence: 99%

“…Expression of enzyme activity depends on the Ca 2ϩ -facilitated dissociation of A 2 Ј from the carrier B 2 subunits and on a concerted conformational change that unmasks the hidden sulfhydryl catalytic centers for the A 2 * (FXIII a ) cross-linking enzyme. 51,57 Although the other trypsin-like enzymes of the coagulation cascade operate with serine-OH active centers, factor XIIIa functions with a cysteine-SH catalytic residue, assisted by the imidazole ring of a histidine. 58,59 There are remarkable kinetic 60,61 and structural 62 similarities with the papain-calpain family of enzymes, suggesting a common evolutionary ancestor.…”

Section: The Urea-insoluble Clotmentioning

confidence: 99%

Sol Sherry Lecture in Thrombosis

Lóránd

2000

ATVB

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“…Zymogen FXIII has no transglutaminase activity as the catalytic triad is buried deep in the core domain of the enzyme surrounded by two barrel domains, which block the entrance to the active site of the enzyme [4]. Conversion into the active transglutaminase (FXIII-A) is mediated by thrombin and Ca 2+ and involves a large conformational change, which removes the barrel domains from the core region thus allowing the substrates access to the active site [5].…”

Section: Introductionmentioning

confidence: 99%

(±) cis-bisamido epoxides: A novel series of potent FXIII-A inhibitors

Avery

Pease

Smith

et al. 2015

European Journal of Medicinal Chemistry

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A novel class of potent FXIII-A inhibitors containing a (±) cis-bisamido epoxide pharmacophore is described. The compounds display highly potent inhibition of FXIII-A (IC 50 = 5-500 nM) in an in vitro assay. In contrast to other types of previously described covalent transglutaminase inhibitors, the bis-amido epoxides exhibited no measurable reactivity with glutathione, therefore possibly rendering this class of compounds suitable for future in vivo investigations. Additionally, the compounds show selective inhibition for FXIII-A against the cysteine protease, cathepsin S although they proved to have similar potency with a closely related transglutaminase, TGII, to that observed for FXIII-A.

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Dissociation of the subunit structure of fibrin stabilizing factor during activation of the zymogen

Cited by 99 publications

References 16 publications

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms

Sol Sherry Lecture in Thrombosis

(±) cis-bisamido epoxides: A novel series of potent FXIII-A inhibitors

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