ACTIVATION OF HUMAN FACTOR-9 (CHRISTMAS-FACTOR)
ACTIVATION OF HUMAN FACTOR-9 (CHRISTMAS-FACTOR)
复制标题
DOI：
10.1172/jci109073
复制
发表时间：
1978-01-01
影响因子：
15.9
通讯作者：
DAVIE, EW
中科院分区：
文献类型：
--
作者：
DISCIPIO, RG;KURACHI, K;DAVIE, EW
人类因子 IX（圣诞因子）是一种单链血浆糖蛋白（摩尔重量 57,000），参与凝血内在途径的中期。它作为酶原存在于血浆中，并在钙离子存在的情况下被因子 XIa（活化的血浆凝血活酶前体）转化为丝氨酸蛋白酶，因子 IXabeta。在活化反应中，因子 IX 中的两个内部肽键被水解。这些裂解发生在特定的精氨酰-丙氨酸肽键和特定的精氨酰-缬氨酸肽键处。这导致从前体分子的内部区域释放激活肽（摩尔重量约等于11,000）并生成因子IXabeta（摩尔重量约等于46,000）。因子IXabeta由轻链（摩尔重量约等于18,000）和重链（摩尔重量约等于28,000）组成，并且这些链通过二硫键连接在一起。轻链源自前体分子的氨基末端部分并具有Tyr-Asn-Ser-Gly-Lys的氨基末端序列。重链起源于前体分子的羧基末端区域并含有Val-Val-Gly-Gly-Glu的氨基末端序列。因子IXabeta的重链还含有活性位点序列Phe-Cys-Ala-Gly-Phe-His-Glu-Gly-Arg-Asp-Ser-Cys-Gln-Gly-Asp-SER-Gly-Gly-Pro。活性位点丝氨酸残基以大写字母显示。因子 IX 还可通过罗素蝰蛇毒液中的蛋白酶转化为因子 IXaalpha。然而，这种激活反应发生在一个步骤中，并且仅涉及内部精氨酰-缬氨酸肽键的裂解。人抗凝血酶 III 通过形成酶和抑制剂的一对一复合物来抑制人因子 IXabeta。在此反应中，抑制剂与酶的重链紧密结合。这些数据表明，人因子 IX 的激活机制及其被抗凝血酶 III 抑制的机制与先前显示的牛因子 IX 的机制基本相同。
Human Factor IX (Christmas factor) is a single-chain plasma glycoprotein (mol wt 57,000) that participates in the middle phase of the intrinsic pathway of blood coagulation. It is present in plasma as a zymogen and is converted to a serine protease, Factor IXabeta, by Factor XIa (activated plasma thromboplastin antecedent) in the presence of calcium ions. In the activation reaction, two internal peptide bonds are hydrolyzed in Factor IX. These cleavages occur at a specific arginyl-alanine peptide bond and a specific arginyl-valine peptide bond. This results in the release of an activation peptide (mol wt approximately equal to 11,000) from the internal region of the precursor molecule and the generation of Factor IXabeta (mol wt approximately equal to 46,000). Factor IXabeta is composed of a light chain (mol wt approximately equal to 18,000) and a heavy chain (mol wt approximately equal to 28,000), and these chains are held together by a disulfide bond(s). The light chain originates from the amino terminal portion of the precursor molecule and has an amino terminal sequence of Tyr-Asn-Ser-Gly-Lys. The heavy chain originates from the carboxyl terminal region of the precursor molecule and contains an amino terminal sequence of Val-Val-Gly-Gly-Glu. The heavy chain of Factor IXabeta also contains the active site sequence of Phe-Cys-Ala-Gly-Phe-His-Glu-Gly-Arg-Asp-Ser-Cys-Gln-Gly-Asp-SER-Gly-Gly-Pro. The active site serine residue is shown in capital letters. Factor IX is also converted to Factor IXaalpha by a protease from Russell's viper venom. This activation reaction, however, occurs in a single step and involves only the cleavage of the internal arginyl-valine peptide bond. Human Factor IXabeta was inhibited by human antithrombin III by the formation of a one-to-one complex of enzyme and inhibitor. In this reaction, the inhibitor was tightly bound to the heavy chain of the enzyme. These data indicate that the mechanism of activation of human Factor IX and its inhibition by antithrombin III is essentially identical to that previously shown for bovine Factor IX.Images