The interaction of α2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism
The interaction of α2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism
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α2-巨球蛋白与蛋白酶的相互作用的特征和特异性，及其分子机制的假设。
DOI：
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发表时间：
1973
期刊：
影响因子：
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通讯作者：
P. Starkey
中科院分区：
文献类型：
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作者：
A. Barrett;P. Starkey
1. 已知α2-巨球蛋白能结合和抑制多种丝氨酸蛋白酶。我们发现它可以结合巯基和羧基蛋白酶，现在有理由相信α2-巨球蛋白可以结合几乎所有的蛋白酶。2. 放射化学标记的胰蛋白酶、凝乳胰蛋白酶、组织蛋白酶B1和木瓜蛋白酶以大约等摩尔的比例与α2巨球蛋白结合。用活性酶滴定法证实胰蛋白酶的等摩尔结合。3. α - 2巨球蛋白用饱和量的一种蛋白酶进行预处理，可以防止随后与另一种蛋白酶的结合。我们得出结论，每个α2巨球蛋白分子只能与一个蛋白酶分子发生反应。4. α2-巨球蛋白不与外肽酶、非蛋白水解酶或无活性形式的内肽酶发生反应。5. 本文回顾了α - 2巨球蛋白结合和抑制蛋白酶的文献，并结合我们自己的工作，可以看出α - 2巨球蛋白相互作用的几个一般特征。6. 提出了α - 2巨球蛋白与蛋白酶相互作用的分子机制模型。这表明该酶在大球蛋白的敏感区域切割肽键，从而导致α2大球蛋白分子的构象变化，从而不可逆地捕获该酶。底物进入酶的活性位点受到立体阻碍，引起抑制，这种抑制在大底物分子中最为明显。7. 讨论了α2巨球蛋白独特的结合特性可能具有的生理意义。
1. α2-Macroglobulin is known to bind and inhibit a number of serine proteinases. We show that it binds thiol and carboxyl proteinases, and there is now reason to believe that α2-macroglobulin can bind essentially all proteinases. 2. Radiochemically labelled trypsin, chymotrypsin, cathepsin B1 and papain are bound by α2-macroglobulin in an approximately equimolar ratio. Equimolar binding was confirmed for trypsin by activesite titration. 3. Pretreatment of α2-macroglobulin with a saturating amount of one proteinase prevented the subsequent binding of another. We conclude that each molecule of α2-macroglobulin is able to react with one molecule of proteinase only. 4. α2-Macroglobulin did not react with exopeptidases, non-proteolytic hydrolases or inactive forms of endopeptidases. 5. The literature on binding and inhibition of proteinases by α2-macroglobulin is reviewed, and from consideration of this and our own work several general characteristics of the interaction can be discerned. 6. A model is proposed for the molecular mechanism of the interaction of α2-macroglobulin with proteinases. It is suggested that the enzyme cleaves a peptide bond in a sensitive region of the macroglobulin, and that this results in a conformational change in the α2-macroglobulin molecule that traps the enzyme irreversibly. Access of substrates to the active site of the enzyme becomes sterically hindered, causing inhibition that is most pronounced with large substrate molecules. 7. The possible physiological importance of the unique binding characteristics of α2-macroglobulin is discussed.