5CFI

Structural and functional attributes of malaria parasite Ap4A hydrolase

5CFI の概要

• エントリーDOI: 10.2210/pdb5cfi/pdb
• 関連するPDBエントリー: 3U53 5CFJ
• 分子名称: BIS(5'-nucleosyl)-tetraphosphatase (Diadenosine tetraphosphatase), putative (2 entities in total)
• 機能のキーワード: ap4a, nudix hydrolyse, plasmodium, purinergic, hydrolase
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 71100.70

構造登録者

Sharma, A.,Yogavel, M.,Sharma, A. (登録日: 2015-07-08, 公開日: 2016-02-10, 最終更新日: 2024-03-20)

主引用文献

Sharma, A.,Yogavel, M.,Sharma, A.
Structural and functional attributes of malaria parasite diadenosine tetraphosphate hydrolase
Sci Rep, 6:19981-19981, 2016

PubMed Abstract: Malaria symptoms are driven by periodic multiplication cycles of Plasmodium parasites in human red blood corpuscles (RBCs). Malaria infection still accounts for ~600,000 annual deaths, and hence discovery of both new drug targets and drugs remains vital. In the present study, we have investigated the malaria parasite enzyme diadenosine tetraphosphate (Ap4A) hydrolase that regulates levels of signalling molecules like Ap4A by hydrolyzing them to ATP and AMP. We have tracked the spatial distribution of parasitic Ap4A hydrolase in infected RBCs, and reveal its unusual localization on the infected RBC membrane in subpopulation of infected cells. Interestingly, enzyme activity assays reveal an interaction between Ap4A hydrolase and the parasite growth inhibitor suramin. We also present a high resolution crystal structure of Ap4A hydrolase in apo- and sulphate- bound state, where the sulphate resides in the enzyme active site by mimicking the phosphate of substrates like Ap4A. The unexpected infected erythrocyte localization of the parasitic Ap4A hydrolase hints at a possible role of this enzyme in purinerigic signaling. In addition, atomic structure of Ap4A hydrolase provides insights for selective drug targeting.

PubMed: 26829485
DOI: 10.1038/srep19981

実験手法

X-RAY DIFFRACTION (2.6 Å)