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通过分析一个包含青蛙、乌龟和鸵鸟抗凝血酶的扩展序列数据库,深入了解抗凝血酶功能的关键残基。

Insight into residues critical for antithrombin function from analysis of an expanded database of sequences that includes frog, turtle, and ostrich antithrombins.

作者信息

Backovic Marija, Gettins Peter G W

机构信息

Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612-4316, USA.

出版信息

J Proteome Res. 2002 Jul-Aug;1(4):367-73. doi: 10.1021/pr025515z.

DOI:10.1021/pr025515z
PMID:12645893
Abstract

Complete sequences were determined for frog, turtle, and ostrich antithrombins. Protein sequence comparisons with the other 10 known antithrombin sequences and with sequences of other serpins have provided striking evidence for the conservation of the heparin activation mechanism and new insight into those residues important for heparin binding, for heparin activation, and for reactive center loop function, as well as an indication of which glycosylation sites might be needed for function. Importantly, an understanding of, as yet, poorly understood antithrombin-protein interactions will be greatly aided by this expanded database and comparative analysis.

摘要

已测定青蛙、乌龟和鸵鸟抗凝血酶的完整序列。将这些蛋白质序列与其他10种已知抗凝血酶序列以及其他丝氨酸蛋白酶抑制剂的序列进行比较,为肝素激活机制的保守性提供了显著证据,并对肝素结合、肝素激活、反应中心环功能重要的残基有了新的认识,还指出了哪些糖基化位点可能对功能是必需的。重要的是,这个扩展的数据库和比较分析将极大地有助于理解目前仍了解甚少的抗凝血酶与蛋白质的相互作用。

相似文献

1
Insight into residues critical for antithrombin function from analysis of an expanded database of sequences that includes frog, turtle, and ostrich antithrombins.通过分析一个包含青蛙、乌龟和鸵鸟抗凝血酶的扩展序列数据库,深入了解抗凝血酶功能的关键残基。
J Proteome Res. 2002 Jul-Aug;1(4):367-73. doi: 10.1021/pr025515z.
2
Critical role of the linker region between helix D and strand 2A in heparin activation of antithrombin.
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Antithrombin and heparin.抗凝血酶与肝素。
Mol Med Today. 1995 Aug;1(5):226-31. doi: 10.1016/s1357-4310(95)91494-3.
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Biological implications of a 3 A structure of dimeric antithrombin.二聚体抗凝血酶3A结构的生物学意义
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Conformational changes in serpins: II. The mechanism of activation of antithrombin by heparin.丝氨酸蛋白酶抑制剂的构象变化:II. 肝素激活抗凝血酶的机制。
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The antithrombin P1 residue is important for target proteinase specificity but not for heparin activation of the serpin. Characterization of P1 antithrombin variants with altered proteinase specificity but normal heparin activation.抗凝血酶的P1残基对靶蛋白酶特异性很重要,但对丝氨酸蛋白酶抑制剂的肝素激活不重要。具有改变的蛋白酶特异性但肝素激活正常的P1抗凝血酶变体的表征。
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The conformational activation of antithrombin. A 2.85-A structure of a fluorescein derivative reveals an electrostatic link between the hinge and heparin binding regions.
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Conformational equilibrium of the reactive center loop of antithrombin examined by steady state and time-resolved fluorescence measurements: consequences for the mechanism of factor Xa inhibition by antithrombin-heparin complexes.通过稳态和时间分辨荧光测量研究抗凝血酶反应中心环的构象平衡:抗凝血酶-肝素复合物抑制因子Xa机制的影响
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Salmon antithrombin has only three carbohydrate side chains, and shows functional similarities to human beta-antithrombin.鲑鱼抗凝血酶只有三条碳水化合物侧链,并且与人类β-抗凝血酶表现出功能相似性。
Eur J Biochem. 2000 Mar;267(6):1651-7. doi: 10.1046/j.1432-1327.2000.01171.x.

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Conformational activation of antithrombin by heparin involves an altered exosite interaction with protease.
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