Nuclear gyrB encodes a functional subunit of the Plasmodium falciparum gyrase that is involved in apicoplast DNA replication

详细信息    查看全文

• 作者：E.V.S. Raghu Ram ; Ambrish Kumar ; Subir Biswas ; Ashutosh Kumar ; Sushma Chaubey ; Mohammad Imran Siddiqi ; Saman Habib
• 关键词：Plasmodium falciparum ; Apicoplast ; Replication ; Gyrase ; Novobiocin
• 刊名：Molecular and Biochemical Parasitology
• 出版年：2007
• 出版时间：July 2007
• 年：2007
• 卷：154
• 期：1
• 页码：30-39
• 全文大小：1461 K

文摘

The DNA replication machinery of the Plasmodium falciparum apicoplast is a validated drug target. Nuclear-encoded gyrase subunits are predicted to play a critical role in maintaining DNA topology during the D-loop/bi-directional ori replication process of the parasite. We show the presence of P. falciparum gyrase subunits in parasite lysates by using antibodies generated against recombinant gyrase A and B. The ATPase activity of PfGyrB was inhibited by novobiocin that also caused parasite death in culture. Reduction of apicoplast/nuclear DNA ratio in the presence of novobiocin indicated that the drug targets apicoplast DNA replication. Molecular modeling of gyrase A and B subunits revealed extensive fold conservation with the Escherichia coli counterparts as well as the presence of a long disordered loop adjacent to the ATPase domain of PfGyrB. Our results have implications for development of PfGyrB as a drug target against malaria.