Role of calcium ion in the generation of factor XIII activity.
The involvement of calcium ion in the activation of both plasma factor XIII (alpha 2 beta 2) and platelet factor XIII (alpha 2) was investigated. The second-order dependence of the rate constant for exposure of the active-site thiol group of alpha-thrombin-cleaved plasma factor XIII (alpha 2'beta 2) on the concentration of calcium ion suggested that the binding of two calcium ions is required for transformation of the alpha 2'beta 2 tetramer to enzymatically active factor XIIIa. Fibrinogen, previously reported to lower the calcium ion concentration required for efficient activation of alpha 2'beta 2 [Credo, R. B., Curtis, C. G., & Lorand, L. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 4234-4237], was found in the present study to increase the rate of exposure of the active-site thiol group. Whereas calcium ion is required for exposure of the active-site thiol group in cleaved plasma factor XIII (alpha 2'beta 2), exposure of an active-site thiol group in cleaved platelet factor XIII (alpha 2') occurs in the absence of calcium ion. The rate constant (2.2 x 10(5) M-1 s-1) for alpha-thrombin-catalyed exposure of the active-site thiol group of platelet factor XIII zymogen (alpha 2) in the presence of calcium ion was greater than the rate constant (0.7 x 10(5) M-1 s-1) determined in the absence of calcium ion.(ABSTRACT TRUNCATED AT 250 WORDS)
Hornyak
T J
TJ
Department of Biological Chemistry, University of Michigan, Ann Arbor, 48109-0606.
Shafer
J A
JA
D000494:Allosteric Regulation; D001665:Binding Sites; D001777:Blood Coagulation; D002118:Calcium / Q000097:blood*; D005176:Factor XIII / Q000378:metabolism*; D006801:Humans; D007460:Iodoacetamide / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D015539:Platelet Activation; D013438:Sulfhydryl Compounds / Q000097:blood; D013917:Thrombin / Q000378:metabolism
D013438:Sulfhydryl Compounds; D005176:Factor XIII; D013917:Thrombin; D002118:Calcium; D007460:Iodoacetamide