Latent α1-Antichymotrypsin
Latent α1-Antichymotrypsin
复制标题
潜伏α1-抗胰蛋白酶
DOI：
--
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发表时间：
1998
影响因子：
4.8
通讯作者：
D. Lomas
中科院分区：
文献类型：
--
作者：
Wun;D. Lomas
α1-抗糜蛋白酶是一种急性时相蛋白，可保护组织免受蛋白水解酶的损伤，但先前的研究表明，慢性支气管炎和肺气肿患者肺内的α1-抗糜蛋白酶是完整的，但作为抑制剂是无活性的。采用硫酸铵分级分离，然后用蓝色琼脂糖和DNA-Sepharose层析从30名健康献血者的血浆中分离出少量完整的、单体的但无活性的α1-抗糜蛋白酶。该物种具有更高的DNA结合亲和力，阳极电泳迁移率比天然α1-抗糜蛋白酶，对热变性，8 m尿素，7 m盐酸胍构象稳定。该蛋白不能接受合成的反应环肽，并且反应环在P5-P4键处对蛋白水解裂解具有抗性，但可以在P1′和P3′之间裂解。这些数据表明，这种新的α1-抗胰凝乳蛋白酶的构象类似于晶体学确定的潜在丝氨酸蛋白酶抑制剂，纤溶酶原激活物抑制剂-1和抗凝血酶。肺灌洗液中的α1-抗胰凝乳蛋白酶与假定的潜伏α1-抗胰凝乳蛋白酶具有相同的电泳迁移率，表明这是先前在慢性支气管炎和肺气肿患者肺中描述的无活性构象。α1-抗糜蛋白酶在肺内从活性状态到非活性状态的构象转变可能在慢性肺病的发病机制中起重要作用。
α1-Antichymotrypsin is an acute phase protein that protects the tissues from damage by proteolytic enzymes, but previous studies have shown that α1-antichymotrypsin within the lungs of patients with chronic bronchitis and emphysema is intact but inactive as an inhibitor. Ammonium sulfate fractionation followed by blue Sepharose and DNA-Sepharose chromatography was used to isolate small amounts of intact, monomeric but inactive α1-antichymotrypsin from the plasma of 30 healthy blood donors. This species had a higher DNA binding affinity with more anodal electrophoretic mobility than native α1-antichymotrypsin and was conformationally stable against thermal denaturation, 8 m urea, and 7 mguanidinium chloride. The protein was unable to accept synthetic reactive loop peptides, and the reactive loop was resistant to proteolytic cleavage at the P5–P4 bond but could be cleaved between P1′ and P3′. These data suggest that this new α1-antichymotrypsin species was in a conformation similar to those of the crystallographically determined latent serpins, plasminogen activator inhibitor-1 and antithrombin. α1-Antichymotrypsin from lung lavage migrated with the same electrophoretic mobility as the putative latent α1-antichymotrypsin, suggesting that this is the inactive conformation described previously in the lungs of patients with chronic bronchitis and emphysema. This conformational transition of α1-antichymotrypsin, from an active to an inactive state, within the lung may play an important role in the pathogenesis of chronic lung disease.
内皮细胞产生纤溶酶原激活剂的潜在抑制剂，可以被变性剂激活。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hekman,CM;Loskutoff,DJ
通讯作者：
Loskutoff,DJ
单链尿激酶和纤溶酶原激活剂抑制剂 1 型的相互作用。
DOI：
10.1074/jbc.270.34.20032
发表时间：
1995
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Manchanda,N;Schwartz,BS
通讯作者：
Schwartz,BS
影响因子：
2.9
作者：
MAST, AE;ENGHILD, JJ;SALVESEN, G
通讯作者：
SALVESEN, G