8rtf | pdb_00008rtf

Crystal structure of Trypanosoma congolense pyruvate kinase in complex with a single-domain antibody (TcoPYK-sdAb42)

spinqualitylabelsall models 8rtf, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8rtf is a 12 chain structure with sequence from Trypanosoma congolense and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G0UYF4_TRYCI Publication Abstract from PubMed African trypanosomes are the causative agents of neglected tropical diseases affecting both humans and livestock. Disease control is highly challenging due to an increasing number of drug treatment failures. African trypanosomes are extracellular, blood-borne parasites that mainly rely on glycolysis for their energy metabolism within the mammalian host. Trypanosomal glycolytic enzymes are therefore of interest for the development of trypanocidal drugs. Here, we report the serendipitous discovery of a camelid single-domain antibody (sdAb aka Nanobody) that selectively inhibits the enzymatic activity of trypanosomatid (but not host) pyruvate kinases through an allosteric mechanism. By combining enzyme kinetics, biophysics, structural biology, and transgenic parasite survival assays, we provide a proof-of-principle that the sdAb-mediated enzyme inhibition negatively impacts parasite fitness and growth. Allosteric inhibition of trypanosomatid pyruvate kinases by a camelid single-domain antibody.,Pinto Torres JE, Claes M, Hendrickx R, Yuan M, Smiejkowska N, Van Wielendaele P, Hacisuleyman A, De Winter H, Muyldermans S, Michels PAM, Walkinshaw MD, Versees W, Caljon G, Magez S, Sterckx YG Elife. 2025 Mar 31;13:RP100066. doi: 10.7554/eLife.100066. PMID:40163365 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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