Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. Evidence for defects affecting the latent catalytic site.
Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. Evidence for defects affecting the latent catalytic site.
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B 型血友病的三种异常因子 IX 变异（Bm 埃尔西诺湖、长滩和洛杉矶）的特征。
DOI：
10.1172/jci111700
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Bajaj,SP
中科院分区：
文献类型：
--
作者：
Usharani,P;Warn-Cramer,BJ;Kasper,CK;Bajaj,SP
从三个不相关的严重B型血友病家族的血浆中分离出异常因子IX变体蛋白，这些家族此前已被证明含有与正常因子IX免疫学相似的功能受损分子。研究的家庭是：（1）牛脑凝血酶原时间显著延长的患者，命名为因子IX Bm埃尔西诺湖（IXBmLE）;（B）三名牛脑凝血酶原时间中度延长的患者（兄弟），命名为因子IX长滩（IXLB）;和（c）牛脑凝血酶原时间正常的患者，命名为因子IX洛杉矶（IXLA）。每个变异分子与正常的因子IX（IXN）在十二烷基硫酸钠和非变性碱性凝胶电泳。所有三种变体蛋白在其氨基酸组成、等电点、碳水化合物分布和γ-羧基谷氨酸残基的数量方面与IXN没有区别。每种变体蛋白都经历了因子XIa/Ca 2+和因子VIIa/Ca 2 +/组织因子的类似切割模式，并以与IXN相似的速率被激活。所有三种变体蛋白质也与抗IXN单克隆抗体反应，该抗体干扰活化的IXN（IXaN）与凝血酶处理的因子VIIIC的结合。然而，与IXaN相反，裂解的IXBmLE具有可忽略的活性（约0.2%），并且裂解形式的IXLA和IXLB在与抗凝血酶-III/肝素结合以及在活化因子VII（加上Ca 2+和磷脂）或因子X（加上Ca 2+和磷脂）+/-因子VIII中具有显著降低的活性（约5-6%）。这些数据，放在一起，强烈表明，在这三种变体蛋白质的缺陷附近或内的潜在催化位点。这导致裂解的IXBmLE分子的催化活性几乎完全丧失，裂解的IXLA和IXLB分子的催化活性丧失约95%。
Abnormal factor IX variant proteins were isolated from the plasmas of three unrelated severe hemophilia-B families that had been previously shown to contain functionally impaired molecules immunologically similar to normal factor IX. The families studied were: (1) a patient with markedly prolonged ox brain prothrombin time, designated factor IX Bm Lake Elsinore (IXBmLE); (b) three patients (brothers) with moderately prolonged ox brain prothrombin time, designated factor IX Long Beach (IXLB); and (c) a patient with normal ox brain prothrombin time designated factor IX Los Angeles (IXLA). Each variant molecule comigrates with normal factor IX (IXN) both in the sodium dodecyl sulfate and in the nondenaturing alkaline gel electrophoresis. All three variant proteins are indistinguishable from IXN in their amino acid compositions, isoelectric points, carbohydrate distributions and number of gamma-carboxyglutamic acid residues. Each variant protein undergoes a similar pattern of cleavage by factor XIa/Ca2+ and by factor VIIa/Ca2+/tissue factor, and is activated at a rate similar to that observed for IXN. All of the three variant proteins also react with an anti-IXN monoclonal antibody that interferes with the binding of activated IXN(IXaN) to thrombin-treated factor VIIIC. However, in contrast to IXaN, the cleaved IXBmLE has negligible activity (approximately 0.2%), and cleaved forms of IXLA and IXLB have significantly reduced activity (approximately 5-6%) in binding to antithrombin-III/heparin, and in activating factor VII (plus Ca2+ and phospholipid) or factor X (plus Ca2+ and phospholipid) +/- factor VIII. These data, taken together, strongly indicate that the defect in these three variant proteins resides near or within the latent catalytic site. This results in virtually a complete loss of catalytic activity of the cleaved IXBmLE molecule and approximately 95% loss of catalytic activity of the cleaved IXLA and IXLB molecules.Images
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特定的氚掺入蛋白质中的γ-羧基谷氨酸中。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Price,PA;Williamson,MK;Epstein,DJ
通讯作者：
Epstein,DJ
B 型血友病的免疫异质性：98 个家族的多中心研究
影响因子：
6.5
作者：
V. Parekh;P. Mannucci;Z. Ruggeri
通讯作者：
Z. Ruggeri
利用 O-(二乙氨基乙基)-Sephadex 和磺丙基-Sephadex 色谱法纯化人因子 VII。
影响因子：
2.9
作者：
L. Rao;S. Bajaj
通讯作者：
S. Bajaj
Chapel Hill IX 因子分子缺陷的鉴定：用组氨酸替代第 145 位的精氨酸。
DOI：
10.1073/pnas.80.14.4200
发表时间：
1983
影响因子：
11.1
作者：
C. Noyes;M. Griffith;H. Roberts;R. Lundblad
通讯作者：
R. Lundblad
人因子 VII 的分离和表征。
影响因子：
4.8
作者：
S. Bajaj;S. Rapaport;S. Brown
通讯作者：
S. Brown