8a12: Difference between revisions

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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/MYOA_PLAF7 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).
[https://www.uniprot.org/uniprot/MYOA_PLAF7 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).
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== 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<ref>PMID:37308472</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
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Revision as of 11:08, 7 February 2024

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

Structural highlights

8a12 is a 3 chain structure with sequence from Plasmodium falciparum. 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:, , , ,
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).

8a12, resolution 2.03Å

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OCA
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