2w41

Publication Abstract from PubMed

Summary Malaria pathology is caused by multiplication of asexual parasites within erythrocytes, whereas mosquito transmission of malaria is mediated by sexual precursor cells (gametocytes). Microarray analysis identified glycerol kinase (GK) as the second most highly upregulated gene in Plasmodium falciparum gametocytes with no expression detectable in asexual blood stage parasites. Phosphorylation of glycerol by GK is the rate-limiting step in glycerol utilisation. Deletion of this gene from P. falciparum had no effect on asexual parasite growth, but surprisingly also had no effect on gametocyte development or exflagellation suggesting that these life cycle stages do not utilise host-derived glycerol as a carbon source. Kinetic studies of purified PfGK showed that the enzyme is not regulated by fructose 1,6 bisphosphate. The high-resolution crystal structure of P. falciparum glycerol kinase, the first of a eukaryotic GK, reveals two domains embracing a capacious ligand-binding groove. In the complexes of PfGK with glycerol and ADP, we observed closed and open forms of the active site, respectively. The 27 degrees domain opening is larger than in orthologous systems and exposes an extensive surface with potential for exploitation in selective inhibitor design should the enzyme prove to be essential in vivo either in the human or in the mosquito.

Structure and non-essential function of glycerol kinase in Plasmodium falciparum blood stages.,Schnick C, Polley SD, Fivelman QL, Ranford-Cartwright LC, Wilkinson SR, Brannigan JA, Wilkinson AJ, Baker DA Mol Microbiol. 2008 Nov 24. PMID:19040641^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.