Effects of Val34Leu and Val35Leu polymorphism on the enzyme activity of the coagulation factor XIII-A
Experimental & Molecular Medicine
; : 385-390, 2002.
Article
in En
| WPRIM
| ID: wpr-160901
Responsible library:
WPRO
ABSTRACT
Change in fibrin stabilizing activity of factor XIII A subunit (FXIII-A) caused by a specific mutation, Val34Leu, is recently implicated to incidences of pathophysiology of thrombosis. In an effort to understand the effect of Val34Leu on enhanced catalytic role of FXIII-A, wild type human factor XIII A (HFXIII-A) and mutant HFXIII-A: HFXIII-A (V34L), HFXIII-A (V35L) and HFXIII-A (V34L/V35L) cDNA were expressed in E.coli system where the purified recombinant FXIII-A (rFXIII-A) showed a similar specific transglutaminase activity comparable to the human native FXIII-A from platelet. Using these rFXIII-A mutants, the activation kinetics by thrombin and the enzymatic properties of the activated rFXIII-A were characterized. rFXIII-A (V34L) and rFXIII-A (V34L/V35L) mutants were activated by thrombin much faster than those of wild type rFXIII-A and V35L variant. However, the activated rFXIII-A and mutants showed the identical catalytic efficiency as measured by in vitro assay. These results suggest that ready activation caused by a specific mutation of neighboring thrombin cleavage site(s) in the activation peptide of FXIII-A like V34L resulted in the real-time amount of the activated factor XIII-A that could influence the outcome of fibrin stabilization in vivo such as alpha2- plasmin inhibitor crosslinking to fibrin, a reaction known to be dependent on the initial concentration of active factor-XIII-A.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Polymorphism, Genetic
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Valine
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Blood Coagulation Tests
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Recombinant Proteins
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Factor XIII
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Fibrin
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Thrombin
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Immunoblotting
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Catalysis
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Mutagenesis, Site-Directed
Limits:
Humans
Language:
En
Journal:
Experimental & Molecular Medicine
Year:
2002
Type:
Article