8RTF

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

Summary for 8RTF

• Entry DOI: 10.2210/pdb8rtf/pdb
• Descriptor: Pyruvate kinase, Camelid single-domain antibody 42 (sdAb42), GLYCEROL, ... (4 entities in total)
• Functional Keywords: pyruvate kinase, single-domain antibody, transferase
• Biological source: Trypanosoma congolense; More
• Total number of polymer chains: 12
• Total formula weight: 437967.73

Authors

Sterckx, Y.G.-J. (deposition date: 2024-01-26, release date: 2025-04-16)

Primary citation

Pinto Torres, J.E.,Claes, M.,Hendrickx, R.,Yuan, M.,Smiejkowska, N.,Van Wielendaele, P.,Hacisuleyman, A.,De Winter, H.,Muyldermans, S.,Michels, P.A.M.,Walkinshaw, M.D.,Versees, W.,Caljon, G.,Magez, S.,Sterckx, Y.G.
Allosteric inhibition of trypanosomatid pyruvate kinases by a camelid single-domain antibody.
Elife, 13:-, 2025

PubMed Abstract: 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.

PubMed: 40163365
DOI: 10.7554/eLife.100066

Experimental method

X-RAY DIFFRACTION (2.8 Å)