Brömme Dieter, Nallaseth Ferez S, Turk Boris
Mount Sinai School of Medicine, Department of Human Genetics, New York, NY 10029-6574, USA.
Methods. 2004 Feb;32(2):199-206. doi: 10.1016/s1046-2023(03)00212-3.
Papain-like cysteine proteases are the most numerous family of the cysteine protease class. They are expressed throughout the animal and plant kingdoms as well as in viruses and bacteria. More recently, this protease family has drawn attention as a potential pharmaceutical drug target in diseases characterized by excessive extracellular matrix degradation such as in osteoporosis, arthritis, vascular diseases, and cancer. Moreover, papain-like cysteine proteases have been identified as critical components of the life cycle and invasive potential of various human and live stock pathogens as well as major allergens. Therefore, this protease class is rigorously studied and requires sufficient amounts of protease protein to analyze structure-activity relationships, their 3-D structures as well as to screen for and optimize potent and selective inhibitors. This review summarizes approaches to generate active papain-like cysteine proteases by heterologous expression in a variety of expression systems.
木瓜蛋白酶样半胱氨酸蛋白酶是半胱氨酸蛋白酶家族中数量最多的一类。它们在动物界、植物界以及病毒和细菌中均有表达。最近，这个蛋白酶家族作为潜在的药物靶点受到关注，这些疾病的特征是细胞外基质过度降解，如骨质疏松症、关节炎、血管疾病和癌症。此外，木瓜蛋白酶样半胱氨酸蛋白酶已被确定为各种人类和家畜病原体生命周期及侵袭潜力的关键组成部分，也是主要的过敏原。因此，对这类蛋白酶进行了深入研究，需要足够量的蛋白酶蛋白来分析结构-活性关系、其三维结构，以及筛选和优化强效和选择性抑制剂。本综述总结了通过在多种表达系统中进行异源表达来产生活性木瓜蛋白酶样半胱氨酸蛋白酶的方法。
