Hornyak T J, Shafer J A
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109-0606.
Biochemistry. 1992 Jan 21;31(2):423-9. doi: 10.1021/bi00117a017.
Factor XIIIa (a2') is a homodimeric transglutaminase that is formed via limited alpha-thrombin-catalyzed proteolysis of the platelet (a2) or plasma (a2b2) factor XIII zymogen in a reaction that results in proteolytic removal of a 37-aminoacyl residue peptide from the N-terminus of the a chains and exposure of the active-site thiol group in the resulting a' chains of factor XIIIa. In this study, we characterized interactions of factor XIII and factor XIIIa with fibrin, a natural substrate for factor XIIIa and a cofactor for the alpha-thrombin-catalyzed activation of plasma factor XIII. The carbamylmethyl derivatives of the active-site thiol group of platelet factor XIII (CMa2) and factor XIIIa (CMa2') were prepared, and their interactions with fibrin were measured. The enzyme-like derivative (CMa2') which contained nicked a' chains bound more tightly to fibrin (Kd = 2.1 microM) than did CMa2 (Kd = 14 microM), the platelet zymogen-like derivative with intact a chains, but the binding of each was weaker than the binding of plasma factor XIII zymogen (a2b2) to fibrin (Kd = 0.20 microM) under the same conditions. Saturation of fibrin with plasma factor XIII zymogen (a2b2) did not affect the binding of CMa2' to fibrin, suggesting that the plasma factor XIII zymogen (a2b2) and the active-site-modified form of factor XIIIa (CMa2') bind to separate, noninteracting sites of fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)
因子 XIIIa（a2'）是一种同二聚体转谷氨酰胺酶，它通过血小板（a2）或血浆（a2b2）因子 XIII 酶原在有限的α-凝血酶催化下进行蛋白水解反应而形成，该反应导致从 a 链的 N 端蛋白水解去除一个 37 个氨基酸残基的肽，并使因子 XIIIa 所得 a'链中的活性位点巯基暴露。在本研究中，我们对因子 XIII 和因子 XIIIa 与纤维蛋白的相互作用进行了表征，纤维蛋白是因子 XIIIa 的天然底物，也是α-凝血酶催化血浆因子 XIII 激活的辅因子。制备了血小板因子 XIII（CMa2）和因子 XIIIa（CMa2'）活性位点巯基的氨甲酰甲基衍生物，并测量了它们与纤维蛋白的相互作用。含有切口 a'链的类酶衍生物（CMa2'）比具有完整 a 链的血小板酶原样衍生物 CMa2（Kd = 14 μM）与纤维蛋白的结合更紧密（Kd = 2.1 μM），但在相同条件下，每种的结合都比血浆因子 XIII 酶原（a2b2）与纤维蛋白的结合（Kd = 0.20 μM）弱。用血浆因子 XIII 酶原（a2b2）使纤维蛋白饱和并不影响 CMa2'与纤维蛋白的结合，这表明血浆因子 XIII 酶原（a2b2）和因子 XIIIa 的活性位点修饰形式（CMa2'）结合到纤维蛋白的不同、不相互作用的位点。（摘要截短于 250 字）
