Bode W, Fernandez-Catalan C, Nagase H, Maskos K
Max-Planck-Institut für Biochemie, Martinsried, Germany.
APMIS. 1999 Jan;107(1):3-10. doi: 10.1111/j.1699-0463.1999.tb01520.x.
Nature uses protein inhibitors as important tools to regulate the proteolytic activity of their target proteinases. Most of these inhibitors for which 3D structures are available are directed towards serine proteinases, interacting with their active-sites in a substrate-like "canonical" manner via an exposed reactive-site loop of conserved conformation. More recently, some non-canonically binding serine proteinase inhibitors, two cysteine proteinase inhibitors, and three zinc endopeptidase inhibitors have been characterized in the free and complexed state, displaying novel mechanisms of inhibition with their target proteinases. These different interaction modes are briefly discussed, with particular emphasis on the interaction between matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs).
自然界将蛋白质抑制剂作为调节其靶蛋白酶蛋白水解活性的重要工具。大多数已获得三维结构的这类抑制剂都作用于丝氨酸蛋白酶，通过保守构象的暴露反应位点环以类似底物的“经典”方式与它们的活性位点相互作用。最近，一些非经典结合的丝氨酸蛋白酶抑制剂、两种半胱氨酸蛋白酶抑制剂和三种锌内肽酶抑制剂已在游离和复合状态下得到表征，显示出与它们的靶蛋白酶的新型抑制机制。本文简要讨论了这些不同的相互作用模式，特别强调了基质金属蛋白酶（MMPs）与其内源性金属蛋白酶组织抑制剂（TIMPs）之间的相互作用。
