Di Scipio R G, Kurachi K, Davie E W
J Clin Invest. 1978 Jun;61(6):1528-38. doi: 10.1172/JCI109073.
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.
人凝血因子IX（克里斯马斯因子）是一种单链血浆糖蛋白（分子量57,000），参与血液凝固内源性途径的中间阶段。它以酶原形式存在于血浆中，在钙离子存在的情况下，被因子XIa（活化的血浆促凝血酶原激酶）转化为丝氨酸蛋白酶因子IXabeta。在激活反应中，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。这导致从前体分子内部区域释放出一个激活肽（分子量约等于11,000），并产生因子IXabeta（分子量约等于46,000）。因子IXabeta由一条轻链（分子量约等于18,000）和一条重链（分子量约等于28,000）组成，这些链通过一个或多个二硫键连接在一起。轻链起源于前体分子的氨基末端部分，其氨基末端序列为Tyr-Asn-Ser-Gly-Lys。重链起源于前体分子的羧基末端区域，包含Val-Val-Gly-Gly-Glu的氨基末端序列。因子IXabeta的重链还包含活性位点序列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用大写字母表示。因子IX也可被罗素蝰蛇毒中的一种蛋白酶转化为因子IXaalpha。然而，这种激活反应是一步发生的，仅涉及内部精氨酰 - 缬氨酸肽键的裂解。人抗凝血酶III通过形成酶与抑制剂的一对一复合物来抑制人因子IXabeta。在这个反应中，抑制剂紧密结合在酶的重链上。这些数据表明，人因子IX的激活机制及其被抗凝血酶III抑制的机制与先前对牛因子IX所显示的机制基本相同。
