期刊
IUCRJ
卷 7, 期 -, 页码 453-461出版社
INT UNION CRYSTALLOGRAPHY
DOI: 10.1107/S2052252520002456
关键词
malaria; Plasmodium vivax; cryo-EM; hexokinase
资金
- Canada Excellence Research Award from the Government of Canada
- NIH Center for Biomedical Excellence (COBRE) [P20GM109094]
Malaria is a devastating disease caused by a protozoan parasite. It affects over 300 million individuals and results in over 400 000 deaths annually, most of whom are young children under the age of five. Hexokinase, the first enzyme in glucose metabolism, plays an important role in the infection process and represents a promising target for therapeutic intervention. Here, cryo-EM structures of two conformational states of Plasmodium vivax hexokinase (PvHK) are reported at resolutions of similar to 3 angstrom. It is shown that unlike other known hexokinase structures, PvHK displays a unique tetrameric organization (similar to 220 kDa) that can exist in either open or closed quaternary conformational states. Despite the resemblance of the active site of PvHK to its mammalian counterparts, this tetrameric organization is distinct from that of human hexokinases, providing a foundation for the structure-guided design of parasite-selective antimalarial drugs.
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