Exploration of structure-function relationships in human factor VIII by site-directed mutagenesis.
Exploration of structure-function relationships in human factor VIII by site-directed mutagenesis.
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通过定点诱变探索人因子 VIII 的结构-功能关系。
DOI：
10.1101/sqb.1986.051.01.066
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Kaufman,RJ
中科院分区：
文献类型：
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作者：
Toole,JJ;Pittman,D;Murtha,P;Wasley,LC;Wang,J;Amphlett,G;Hewick,R;Foster,WB;Kamen,R;Kaufman,RJ
血友病A是一种X-连锁出血性疾病（每100，000例男性中约有10-20例发生），由特定凝血蛋白（因子VIII）缺乏或异常引起。受影响的个体遭受不受控制的出血发作，并且目前用富含源自人血浆的因子VIII的浓缩物治疗。可用的治疗，虽然合理有效，是非常昂贵的，并与有限的感染的风险。因子VIII的功能在凝血级联作为因子IXa的因子X的蛋白水解激活的辅因子。凝血因子VIII参与的凝血途径最终导致纤维蛋白原的蛋白水解裂解，形成不溶性纤维蛋白聚合物。在体内，纤维蛋白沉积与血小板聚集共同作用，以减少受损血管的失血。
Hemophilia A is an X-linked bleeding disorder (which occurs in~ 10-20 males in every 100,000) caused by deficiency or abnormality of a particular clotting protein, factor VIII. Afflicted individuals suffer episodes of uncontrolled bleeding and are currently treated with concentrates rich in factor VIII derived from human plasma. The available therapy, although reasonably effective, is very costly and is associated with a finite risk of infection.Factor VIII functions in the blood-clotting cascade as the cofactor for factor IXa proteolytic activation of factor X. The blood-clotting pathway in which factor VIII participates eventually results in the proteolytic cleavage of fibrinogen to form insoluble fibrin polymers. In vivo, fibrin deposition in conjunction with platelet aggregation act to curtail blood loss from a damaged vessel.