Structural Studies on Functional Abnormality of Fibrinogen and Factor IX

1.血染因子IX Kashihara ： Hemophilia B Kashihara是因子IX抗原中的严重贫血紊乱，但因子IX生物活动被市场上明显减少。一种tryptic peptides isolated from factor IX Kashihara的氨基酸序列分析，该分析表明Val-182已被phe替换。val-to-phe替换出现以精确地隐藏Arg 180-Val 181的清除所需的因子XIa用于激活此zymogen.2。因子IX Kawachinagano ：因子IX Kawachinagano （KWC）是一种突变因子IX蛋白，在患有严重贫血B的患者中首次被识别，该患者拥有46%的正常因子IX抗原和无检测的服装活动。氨基酸序列分析表明，该变异保留了18个氨基酸足以替代精氨酸区域（-4），由谷氨酰胺引起。我们假定这个propeptide的直接干扰与adjacent NH_2-终止符并防止金属衍生物 ... More d适应性变化是正常因素的生物活动的必要条件IX.3。Coagulation factor XII （Hageman factor ）WashManagement D. C. C.：关于一个共同体非正常凝聚因子XII （Hageman因子）的结构研究，因子XII Washington D.。C.，已经被证明是为了识别出缺乏促进者活动的不良反应。对一种tryptic肽的氨基酸序列分析，Cys-571已被序列替换。我们建议摧毁Cys-571-> Cys-540和Cys-571之间的Disulfide Link的形成，并提出了一个改变的决定，即激活站点系列驻地或二级基层绑定站点的结构，因此，导致酶活性的损失。Blocking Factor IX B_M名古屋：一个有这个突变体的病人是由一个有标记的延长的ox Brained Prothrombin时间表征的。Primary structure analysis of the Asp-N peptides revealed that Arg180 is replaced by Trp.我们还发现了Nagoya IX是由alpha-chymotrypsin或大鼠肥大细胞chymase激活的。这些结果表明了对Arg 180的替代的Trp对清除的影响需要因子XIA来激活这种Zymogen，以及替代导致了Hemophilia B_M。Less（低）

1. Blood Clotting Factor IX Kashihara : Hemophilia B Kashihara is a severe hemorrhagic disorder in which the factor IX antigen is present in normal amounts but factor IX biological activity is markedly reduced. Amino acid sequence analysis of one of the tryptic peptides isolated from factor IX Kashihara indicated that Val-182 had been replaced by phe. The val-to-phe replacement appears to sterically hinder the cleavage of Arg 180-Val 181 by factor XIa required for the activation of this zymogen.2. Factor IX Kawachinagano : Factor IX Kawachinagano (KWC) is a mutant factor IX protein initially recognized in a patient with severe hemophilia B, who had 46% of normal factor IX antigen and no detectable clotting activity. Amino acid sequence analysis demonstrated that the mutant retained the propeptide region of 18 amino acid due to a substitution of arginine- (-4) by glutamine. We assumed that this propeptide directly interferes with the adjacent NH_2- terminus and prevents the metal-induce … More d conformational changes which are essential for biological activity of normal factor IX.3. Coagulation factor XII (Hageman factor ) Washington D. C. : Structural studies on a congenital abnormal coagulation factor XII (Hageman factor), factor XII Washington D. C., have been performed to identify the defect responsible for its lack of procoagulant activity. Amino acid sequence analysis of a tryptic peptide indicated that Cys-571 had been replaced by serine. We propose that the Cysー571->Ser replacement destroys the formation of the disulfide linkage between Cys-540 and Cys-571, giving rise to an altered conformation of the active-site serine residue or the secondary substrate-binding site and, thus, leads to the loss of enzyme activity.4. Blood clotting Factor IX B_M Nagoya : A patient with this mutant is characterized by a markedly prolonged ox brained prothrombin time. Primary structure analysis of one of the AspーN peptides revealed that Arg180 is replaced by Trp. We also found that IX Nagoya is activated by alpha- chymotrypsin or rat mast cell chymase. These results indicate that the substitution of Arg180 by Trp impairs the cleavage by factor XIa required for activation of this zymogen and that the substitution causes hemophilia B_M. Less