Birkholtz Lyn-Marie, Blatch Gregory, Coetzer Theresa L, Hoppe Heinrich C, Human Esmaré, Morris Elizabeth J, Ngcete Zoleka, Oldfield Lyndon, Roth Robyn, Shonhai Addmore, Stephens Linda, Louw Abraham I
Department of Biochemistry, University of Pretoria, Pretoria, South Africa.
Malar J. 2008 Oct 1;7:197. doi: 10.1186/1475-2875-7-197.
Malaria remains the world's most devastating tropical infectious disease with as many as 40% of the world population living in risk areas. The widespread resistance of Plasmodium parasites to the cost-effective chloroquine and antifolates has forced the introduction of more costly drug combinations, such as Coartem. In the absence of a vaccine in the foreseeable future, one strategy to address the growing malaria problem is to identify and characterize new and durable antimalarial drug targets, the majority of which are parasite proteins. Biochemical and structure-activity analysis of these proteins is ultimately essential in the characterization of such targets but requires large amounts of functional protein. Even though heterologous protein production has now become a relatively routine endeavour for most proteins of diverse origins, the functional expression of soluble plasmodial proteins is highly problematic and slows the progress of antimalarial drug target discovery. Here the status quo of heterologous production of plasmodial proteins is presented, constraints are highlighted and alternative strategies and hosts for functional expression and annotation of plasmodial proteins are reviewed.
疟疾仍然是世界上最具毁灭性的热带传染病，世界上多达40%的人口生活在危险地区。疟原虫对经济高效的氯喹和抗叶酸药物产生广泛耐药性，这迫使人们采用更昂贵的药物组合，如科泰复。在可预见的未来缺乏疫苗的情况下，解决日益严重的疟疾问题的一个策略是识别和表征新的、持久的抗疟药物靶点，其中大多数是寄生虫蛋白。对这些蛋白质进行生化和构效分析对于此类靶点的表征至关重要，但需要大量的功能性蛋白质。尽管现在对于大多数来源各异的蛋白质来说，异源蛋白质生产已成为一项相对常规的工作，但可溶性疟原虫蛋白质的功能性表达却存在很大问题，这减缓了抗疟药物靶点发现的进程。本文介绍了疟原虫蛋白质异源生产的现状，强调了限制因素，并综述了疟原虫蛋白质功能性表达和注释的替代策略及宿主。
