The methioninase from the alkalithermophile Thermobrachium celere possesses suitable properties for treatment of cancer
Abstract
L-Methionine deprivation for cancer treatment requires pyridoxal 5′-phosphate (PLP)-dependent L-methionine γlyases (MGL) with sustained activity in plasma. We investigated the MGL from the alkaliphilic thermophile Thermobrachium celere (TcMGL), which was compared to that from Pseudomonas putida (PpMGL) as a reference. Catalysis was limited to L-methionine, L-homocysteine, and L-cysteine, with highest catalytic efficiency towards Lmethionine. Binding of apo-TcMGL to PLP results from an endothermic entropy-driven process, contrasting with apo-PpMGL that binds to cofactor following an exothermic enthalpy-driven reaction, as demonstrated with isothermal titration calorimetry. The tetrameric crystal structure of TcMGL revealed a mobile domain adopting open and closed conformations, regulating access of substrate and PLP to the active site. TcMGL exhibited great stability in human plasma in vitro. Half-life of the active enzyme increased from 9.2 h to 66.7 h with increasing PLP concentration, in much greater magnitude than that of PpMGL. Two-way ANOVA demonstrated a highly significant effect on half-lives of enzyme type and PLP concentration. The enzyme eliminated L-methionine from human plasma and exerted potent cytotoxicity against human carcinoma cells in vitro. TcMGL favourable characteristics make it a suitable candidate for treatment of cancer.
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BibTeX
@article{ferchaud2026methioninase,
title = {{The methioninase from the alkalithermophile Thermobrachium celere possesses suitable properties for treatment of cancer}},
author = {Nathan Ferchaud and David Kopečný and Miroslav Peřina and Angélique Boyer and Sihem Hentati and Clément Pontoizeau and Christophe Desterke and Vladimir Kryštof and David Machover and Pierre Briozzo},
journal = {International Journal of Biological Macromolecules},
year = {2026},
month = sep,
doi = {10.1016/j.ijbiomac.2025.147876},
url = {https://agroparistech.hal.science/hal-05636257v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The methioninase from the alkalithermophile Thermobrachium celere possesses suitable properties for treatment of cancer
AU - Nathan Ferchaud
AU - David Kopečný
AU - Miroslav Peřina
AU - Angélique Boyer
AU - Sihem Hentati
AU - Clément Pontoizeau
AU - Christophe Desterke
AU - Vladimir Kryštof
AU - David Machover
AU - Pierre Briozzo
PY - 2026
DA - 2026/09/01
JO - International Journal of Biological Macromolecules
DO - 10.1016/j.ijbiomac.2025.147876
UR - https://agroparistech.hal.science/hal-05636257v1
AB - L-Methionine deprivation for cancer treatment requires pyridoxal 5′-phosphate (PLP)-dependent L-methionine γlyases (MGL) with sustained activity in plasma. We investigated the MGL from the alkaliphilic thermophile Thermobrachium celere (TcMGL), which was compared to that from Pseudomonas putida (PpMGL) as a reference. Catalysis was limited to L-methionine, L-homocysteine, and L-cysteine, with highest catalytic efficiency towards Lmethionine. Binding of apo-TcMGL to PLP results from an endothermic entropy-driven process, contrasting with apo-PpMGL that binds to cofactor following an exothermic enthalpy-driven reaction, as demonstrated with isothermal titration calorimetry. The tetrameric crystal structure of TcMGL revealed a mobile domain adopting open and closed conformations, regulating access of substrate and PLP to the active site. TcMGL exhibited great stability in human plasma in vitro. Half-life of the active enzyme increased from 9.2 h to 66.7 h with increasing PLP concentration, in much greater magnitude than that of PpMGL. Two-way ANOVA demonstrated a highly significant effect on half-lives of enzyme type and PLP concentration. The enzyme eliminated L-methionine from human plasma and exerted potent cytotoxicity against human carcinoma cells in vitro. TcMGL favourable characteristics make it a suitable candidate for treatment of cancer.
SN - 0141-8130
ER -