Van Rompaey L, Proost P, Van den Berghe H, Marynen P
Center for Human Genetics-Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium.
Biochem J. 1995 Nov 15;312 ( Pt 1)(Pt 1):191-5. doi: 10.1042/bj3120191.
Human alpha 2-macroglobulin (alpha 2M) inhibits a broad spectrum of proteases by changing its conformation and physically confining the enzyme. The inhibitory spectrum of alpha 2M is defined by a stretch of 39 amino acids, the bait region, located near the middle of the alpha 2M monomers. To investigate whether a new inhibitory specificity can be introduced by the manipulation of the bait region, recombinant alpha 2M (r alpha 2M) was produced in which the primary cleavage site was replaced by a heptapeptide containing the cleavage specificity of tobacco etch virus (TEV) protease. This protease is not inhibited by wild-type alpha 2M. The r alpha 2M, produced in an episomal expression system, was fully functional and able to inhibit the tobacco etch virus protease according to its normal 'trap' mechanism. The manipulation of the bait region of alpha 2M thus allows the design of new, specific protease inhibitors.
人α2-巨球蛋白（α2M）通过改变其构象并物理性地限制酶来抑制多种蛋白酶。α2M的抑制谱由一段39个氨基酸的序列（诱饵区域）定义，该区域位于α2M单体的中部附近。为了研究通过操纵诱饵区域是否可以引入新的抑制特异性，制备了重组α2M（rα2M），其中主要切割位点被含有烟草蚀纹病毒（TEV）蛋白酶切割特异性的七肽所取代。这种蛋白酶不被野生型α2M抑制。在游离表达系统中产生的rα2M具有完全功能，并且能够根据其正常的“陷阱”机制抑制烟草蚀纹病毒蛋白酶。因此，对α2M诱饵区域的操纵允许设计新的、特异性的蛋白酶抑制剂。
