2w41

Crystal structure of Plasmodium falciparum glycerol kinase with ADP

spinqualitylabelsall models 2w41, resolution 2.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2w41 is a 2 chain structure with sequence from Plaf7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, EDO Related: 2w40 Activity: Glycerol kinase, with EC number 2.7.1.30 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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