Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum
Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum
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DOI：
10.1074/jbc.274.45.32411
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发表时间：
1999-11-05
影响因子：
4.8
通讯作者：
Goldberg, DE
中科院分区：
文献类型：
--
作者：
Eggleson, KK;Duffin, KL;Goldberg, DE
疟疾寄生虫恶性疟原虫降解其酸性食物液泡中的血红蛋白，以用作主要营养源。从食物液泡中纯化并表征了一种新型金属肽酶活性——falcilysin。 Falcilysin 似乎在血红蛋白蛋白水解途径中的天冬氨酸蛋白酶 plasmepsins I 和 II 以及半胱氨酸蛋白酶 falcipain 的下游发挥作用。它无法裂解血红蛋白或变性珠蛋白，但很容易破坏血红蛋白的肽片段。沿血红蛋白 α 和 β 链的 Falcilysin 裂解位点具有极性特征，带电残基位于 P1 和/或 P4' 位置。相反，plasmepsins I 和 II 以及 falcipain 更喜欢易断键周围的疏水残基。编码falcilysin的基因已被克隆。其编码序列表现出 ME 家族 M16 金属肽酶的特征，包括“反向”HXXEH 活性位点基序，Falcilysin 与 M16 家族成员（如胰岛素、线粒体加工肽酶、nardilysin 和 Pitrilysin）以及数据库假设的潜在 M16 家族成员蛋白质具有主要结构特征。 falcilysin 的表征增加了我们对恶性疟原虫血红蛋白分解代谢和不寻常的 M16 金属肽酶家族的理解。
The malaria parasite Plasmodium falciparum degrades hemoglobin in its acidic food vacuole for use as a major nutrient source. A novel metallopeptidase activity, falcilysin, was purified from food vacuoles and characterized. Falcilysin appears to function downstream of the aspartic proteases plasmepsins I and II and the cysteine protease falcipain in the hemoglobin proteolytic pathway. It is unable to cleave hemoglobin or denatured globin but readily destroys peptide fragments of hemoglobin. Falcilysin cleavage sites along the alpha and beta chains of hemoglobin are polar in character, with charged residues located in the P1 and/or P4' positions. In contrast, plasmepsins I and II and falcipain prefer hydrophobic residues around the scissile bond. The gene encoding falcilysin has been cloned. Its coding sequence exhibits features characteristic of clan ME family M16 metallopeptidases, including an "inverted" HXXEH active site motif, Falcilysin shares primary structural features with M16 family members such as insulysin, mitochondrial processing peptidase, nardilysin, and pitrilysin as well as with data base hypothetical proteins that are potential M16 family members. The characterization of falcilysin increases our understanding of hemoglobin catabolism in P. falciparum and the unusual M16 family of metallopeptidases.