Characterization of Plasmodium falciparum Pantothenate Kinase and Identification of Its Inhibitors From Natural Products

Arif Nurkanto, Ghulam Jeelani, Herbert J. Santos, Yulia Rahmawati, Mihoko Mori, Yumi Nakamura, Kana Goto, Yoko Saikawa, Takeshi Annoura, Yuzuru Tozawa, Takaya Sakura, Daniel Ken Inaoka, Kazuro Shiomi, Tomoyoshi Nozaki

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Coenzyme A (CoA) is a well-known cofactor that plays an essential role in many metabolic reactions in all organisms. In Plasmodium falciparum, the most deadly among Plasmodium species that cause malaria, CoA and its biosynthetic pathway have been proven to be indispensable. The first and rate-limiting reaction in the CoA biosynthetic pathway is catalyzed by two putative pantothenate kinases (PfPanK1 and 2) in this parasite. Here we produced, purified, and biochemically characterized recombinant PfPanK1 for the first time. PfPanK1 showed activity using pantetheine besides pantothenate, as the primary substrate, indicating that CoA biosynthesis in the blood stage of P. falciparum can bypass pantothenate. We further developed a robust and reliable screening system to identify inhibitors using recombinant PfPanK1 and identified four PfPanK inhibitors from natural compounds.

本文言語English
論文番号639065
ジャーナルFrontiers in cellular and infection microbiology
11
DOI
出版ステータスPublished - 2021 3 9

ASJC Scopus subject areas

  • 微生物学
  • 免疫学
  • 微生物学(医療)
  • 感染症

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