8RTF

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

8RTF の概要

• エントリーDOI: 10.2210/pdb8rtf/pdb
• 分子名称: Pyruvate kinase, Camelid single-domain antibody 42 (sdAb42), GLYCEROL, ... (4 entities in total)
• 機能のキーワード: pyruvate kinase, single-domain antibody, transferase
• 由来する生物種: Trypanosoma congolense; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 437967.73

構造登録者

Sterckx, Y.G.-J. (登録日: 2024-01-26, 公開日: 2025-04-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.8 Å)