8a12

Plasmodium falciparum Myosin A full-length, post-rigor state complexed to Mg.ATP-gamma-S

spinqualitylabelsall models 8a12, resolution 2.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8a12 is a 3 chain structure with sequence from Plasmodium falciparum and Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.03Å Ligands: ADP, EDO, MG, SEP, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MYOA_PLAF7 Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity). Publication Abstract from PubMed Malaria results in more than 500,000 deaths per year and the causative Plasmodium parasites continue to develop resistance to all known agents, including different antimalarial combinations. The class XIV myosin motor PfMyoA is part of a core macromolecular complex called the glideosome, essential for Plasmodium parasite mobility and therefore an attractive drug target. Here, we characterize the interaction of a small molecule (KNX-002) with PfMyoA. KNX-002 inhibits PfMyoA ATPase activity in vitro and blocks asexual blood stage growth of merozoites, one of three motile Plasmodium life-cycle stages. Combining biochemical assays and X-ray crystallography, we demonstrate that KNX-002 inhibits PfMyoA using a previously undescribed binding mode, sequestering it in a post-rigor state detached from actin. KNX-002 binding prevents efficient ATP hydrolysis and priming of the lever arm, thus inhibiting motor activity. This small-molecule inhibitor of PfMyoA paves the way for the development of alternative antimalarial treatments. Mechanism of small molecule inhibition of Plasmodium falciparum myosin A informs antimalarial drug design.,Moussaoui D, Robblee JP, Robert-Paganin J, Auguin D, Fisher F, Fagnant PM, Macfarlane JE, Schaletzky J, Wehri E, Mueller-Dieckmann C, Baum J, Trybus KM, Houdusse A Nat Commun. 2023 Jun 12;14(1):3463. doi: 10.1038/s41467-023-38976-7. PMID:37308472 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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