Phosphofructokinases a and b from mycobacterium tuberculosis display different catalytic properties and allosteric regulation

0539494 - ÚOCHB 2022 RIV CH eng J - Článek v odborném periodiku
Snášel, Jan - Machová, Iva - Šolínová, Veronika - Kašička, Václav - Krečmerová, Marcela - Pichová, Iva
Phosphofructokinases a and b from mycobacterium tuberculosis display different catalytic properties and allosteric regulation.
International Journal of Molecular Sciences. Roč. 22, č. 3 (2021), č. článku 1483. E-ISSN 1422-0067
Grant CEP: GA MŠMT(CZ) EF16_019/0000729
Institucionální podpora: RVO:61388963
Klíčová slova: Mycobacterium tuberculosis * glycolysis * phosphofructokinase A and B * allosteric regulation * enzyme kinetics
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 6.208, rok: 2021
Způsob publikování: Open access
https://doi.org/10.3390/ijms22031483

Tuberculosis (TB) remains one of the major health concerns worldwide. Mycobacterium tuberculosis (Mtb), the causative agent of TB, can flexibly change its metabolic processes during different life stages. Regulation of key metabolic enzyme activities by intracellular conditions, allosteric inhibition or feedback control can effectively contribute to Mtb survival under different conditions. Phosphofructokinase (Pfk) is one of the key enzymes regulating glycolysis. Mtb encodes two Pfk isoenzymes, Pfk A/Rv3010c and Pfk B/Rv2029c, which are differently expressed upon transition to the hypoxia-induced non-replicating state of the bacteria. While pfkB gene and protein expression are upregulated under hypoxic conditions, Pfk A levels decrease. Here, we present biochemical characterization of both Pfk isoenzymes, revealing that Pfk A and Pfk B display different kinetic properties. Although the glycolytic activity of Pfk A is higher than that of Pfk B, it is markedly inhibited by an excess of both substrates (fructose-6-phosphate and ATP), reaction products (fructose-1,6-bisphosphate and ADP) and common metabolic allosteric regulators. In contrast, synthesis of fructose-1,6-bisphosphatase catalyzed by Pfk B is not regulated by higher levels of substrates, and metabolites. Importantly, we found that only Pfk B can catalyze the reverse gluconeogenic reaction. Pfk B thus can support glycolysis under conditions inhibiting Pfk A function.
Trvalý link: http://hdl.handle.net/11104/0317591