首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Identification of the primary structural defect in the dysthrombin thrombin Quick I: substitution of cysteine for arginine-382
Authors:R A Henriksen  K G Mann
Institution:Department of Biochemistry, University of Vermont, Burlington 05405.
Abstract:A congenitally dysfunctional form of prothrombin, prothrombin Quick, was isolated from the plasma of an individual with less than 2% of normal prothrombin activity. Following activation of prothrombin Quick, two dysfunctional thrombins, thrombin Quick I and thrombin Quick II, were isolated. Functional characterization of thrombin Quick I indicated an increase in KM and a decrease in kcat, relative to thrombin, for release of fibrinopeptide A. Comparison of kcat/KM for thrombin Quick I to the value obtained for thrombin yielded a relative catalytic efficiency of 0.012 for thrombin Quick I Henriksen, R. A., & Owen, W. G. (1987) J. Biol. Chem. 262, 4664-4669]. Lysyl endopeptidase digestor of reduced and S-carboxymethylated thrombin and thrombin Quick I has resulted in the identification of an altered peptide in this dysthrombin. Edman degradation of the isolated peptide has shown that the altered residue in this protein is Arg-382 which is replaced by Cys. This could result from a point mutation in the Arg codon, CGC, to yield TGC. Together, these results indicate that Arg-382 is a critical residue in determining the specificity of thrombin toward fibrinogen. Similar relative activities for thrombin Quick I in stimulating platelet aggregation, in the release of prostacyclin from human umbilical vein endothelium, and in the release of fibrinopeptide A suggest that these activities of thrombin share the same specificity determinants.
Keywords:
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号