Rotonda J, Nicholson D W, Fazil K M, Gallant M, Gareau Y, Labelle M, Peterson E P, Rasper D M, Ruel R, Vaillancourt J P, Thornberry N A, Becker J W
Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA.
Nat Struct Biol. 1996 Jul;3(7):619-25. doi: 10.1038/nsb0796-619.
Cysteine proteases related to mammalian interleukin-1 beta converting enzyme (ICE) and to its Caenorhabditis elegans homologue, CED-3, play a critical role in the biochemical events that culminate in apoptosis. We have determined the three-dimensional structure of a complex of the human CED-3 homologue CPP32/apopain with a potent tetrapeptide-aldehyde inhibitor. The protein resembles ICE in overall structure, but its S4 subsite is strikingly different in size and chemical composition. These differences account for the variation in specificity between the ICE- and CED-3-related proteases and enable the design of specific inhibitors that can probe the physiological functions of the proteins and disease states with which they are associated.
与哺乳动物白细胞介素-1β转化酶（ICE）及其秀丽隐杆线虫同源物CED-3相关的半胱氨酸蛋白酶，在最终导致细胞凋亡的生化事件中起关键作用。我们已经确定了人类CED-3同源物CPP32/凋亡蛋白酶与一种有效的四肽醛抑制剂复合物的三维结构。该蛋白质在整体结构上与ICE相似，但其S4亚位点在大小和化学组成上有显著差异。这些差异解释了ICE相关蛋白酶和CED-3相关蛋白酶之间特异性的变化，并使得能够设计出特异性抑制剂，用于探究这些蛋白质的生理功能以及它们所关联的疾病状态。
