Details

Autor(en) / Beteiligte

• Wang, Jigang
• Zhang, Chong-Jing
• Chia, Wan Ni
• Loh, Cheryl C Y
• Li, Zhengjun
• Lee, Yew Mun
• He, Yingke
• Yuan, Li-Xia
• Lim, Teck Kwang
• Liu, Min
• Liew, Chin Xia
• Lee, Yan Quan
• Zhang, Jianbin
• Lu, Nianci
• Lim, Chwee Teck
• Hua, Zi-Chun
• Liu, Bin
• Shen, Han-Ming
• Tan, Kevin S W
• Lin, Qingsong

Titel

Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum

Ist Teil von

• Nature communications, 2015-12, Vol.6 (1), p.10111-10111, Article 10111

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The mechanism of action of artemisinin and its derivatives, the most potent of the anti-malarial drugs, is not completely understood. Here we present an unbiased chemical proteomics analysis to directly explore this mechanism in Plasmodium falciparum. We use an alkyne-tagged artemisinin analogue coupled with biotin to identify 124 artemisinin covalent binding protein targets, many of which are involved in the essential biological processes of the parasite. Such a broad targeting spectrum disrupts the biochemical landscape of the parasite and causes its death. Furthermore, using alkyne-tagged artemisinin coupled with a fluorescent dye to monitor protein binding, we show that haem, rather than free ferrous iron, is predominantly responsible for artemisinin activation. The haem derives primarily from the parasite's haem biosynthesis pathway at the early ring stage and from haemoglobin digestion at the latter stages. Our results support a unifying model to explain the action and specificity of artemisinin in parasite killing.