Malaria Biology Laboratory, Queensland Institute of Medical Research, Herston, QLD 4006, Australia.
Trends Biochem Sci. 2010 Jan;35(1):53-61. doi: 10.1016/j.tibs.2009.08.004. Epub 2009 Sep 30.
The neutral aminopeptidases M1 alanyl aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) of the human malaria parasite Plasmodium falciparum are targets for the development of novel anti-malarial drugs. Although the functions of these enzymes remain unknown, they are believed to act in the terminal stages of haemoglobin degradation, generating amino acids essential for parasite growth and development. Inhibitors of both enzymes are lethal to P. falciparum in culture and kill the murine malaria P. chabaudi in vivo. Recent biochemical, structural and functional studies provide the substrate specificity and mechanistic binding data needed to guide the development of more potent anti-malarial drugs. Together with biological studies, these data form the rationale for choosing PfM1AAP and PfM17LAP as targets for anti-malarial development.
人类疟疾寄生虫恶性疟原虫的中性氨肽酶 M1 丙氨酰氨肽酶（PfM1AAP）和 M17 亮氨酰氨肽酶（PfM17LAP）是新型抗疟药物开发的靶点。尽管这些酶的功能尚不清楚，但它们被认为在血红蛋白降解的末端阶段发挥作用，产生对寄生虫生长和发育至关重要的氨基酸。两种酶的抑制剂在培养的恶性疟原虫中都是致命的，并且在体内杀死鼠疟原虫 P. chabaudi。最近的生化、结构和功能研究提供了底物特异性和机制结合数据，为开发更有效的抗疟药物提供了指导。这些数据与生物学研究一起，为选择 PfM1AAP 和 PfM17LAP 作为抗疟药物开发的靶点提供了依据。
