Division of Infectious Diseases, Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Division of Infectious Diseases, Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
J Biol Chem. 2020 Jun 19;295(25):8425-8441. doi: 10.1074/jbc.REV120.009309. Epub 2020 May 4.
Plasmepsins are a group of diverse aspartic proteases in the malaria parasite Their functions are strikingly multifaceted, ranging from hemoglobin degradation to secretory organelle protein processing for egress, invasion, and effector export. Some, particularly the digestive vacuole plasmepsins, have been extensively characterized, whereas others, such as the transmission-stage plasmepsins, are minimally understood. Some ( plasmepsin V) have exquisite cleavage sequence specificity; others are fairly promiscuous. Some have canonical pepsin-like aspartic protease features, whereas others have unusual attributes, including the nepenthesin loop of plasmepsin V and a histidine in place of a catalytic aspartate in plasmepsin III. We have learned much about the functioning of these enzymes, but more remains to be discovered about their cellular roles and even their mechanisms of action. Their importance in many key aspects of parasite biology makes them intriguing targets for antimalarial chemotherapy. Further consideration of their characteristics suggests that some are more viable drug targets than others. Indeed, inhibitors of invasion and egress offer hope for a desperately needed new drug to combat this nefarious organism.
疟原虫中的裂殖体蛋白是一组多样化的天冬氨酸蛋白酶。其功能多种多样，从血红蛋白降解到分泌细胞器蛋白加工，涉及外排、入侵和效应物输出。其中一些，特别是消化液泡裂殖体蛋白，已经得到了广泛的研究，而其他一些，如传播阶段裂殖体蛋白，了解甚少。有些（裂殖体蛋白 V）具有精细的切割序列特异性；而其他的则相当混杂。有些具有典型的胃蛋白酶样天冬氨酸蛋白酶特征，而其他的则具有不寻常的属性，包括裂殖体蛋白 V 的 Nepenthesin 环和裂殖体蛋白 III 中的组氨酸取代了催化天冬氨酸。我们已经了解了这些酶的功能，但它们在细胞中的作用，甚至它们的作用机制，仍有许多有待发现。它们在寄生虫生物学的许多关键方面都很重要，因此成为抗疟化疗的有趣靶点。进一步考虑它们的特征表明，有些比其他的更适合作为药物靶点。事实上，入侵和外排抑制剂为对抗这种恶性生物提供了一种急需的新药的希望。
