0618499 - FGÚ 2026 RIV US eng J - Journal Article
Zimmermannová, Olga - Kubeš, Martin - Przeczková, Tereza - Masrati, G.
Residues R177 and S178 of the human Na+/H+ antiporter NHA2 are involved in its inhibition by the flavonoid phloretin.
FEBS Letters. Roč. 599, č. 6 (2025), s. 901-911. ISSN 0014-5793. E-ISSN 1873-3468
R&D Projects: GA ČR(CZ) GA21-08985S
Institutional support: RVO:67985823
Keywords : human NHA2 * Na+/H+ antiporter * phloretin inhibition * yeast
OECD category: Biochemistry and molecular biology
Impact factor: 3, year: 2023 ; AIS: 1.208, rok: 2023
Method of publishing: Open access
Result website:
https://doi.org/10.1002/1873-3468.15089DOI: https://doi.org/10.1002/1873-3468.15089

The Homo sapiens Na+/H+ antiporter NHA2 (SLC9B2) transports Na+ or Li+ in exchange for protons across cell membranes, and its dysfunction results in various pathologies. The activity of HsNHA2 is specifically inhibited by the flavonoid phloretin. Using bioinformatic modeling, we predicted two amino acids (R177 and S178) as being important for the binding of phloretin to the HsNHA2 molecule. Functional expression of HsNHA2 in Saccharomyces cerevisiae and its site-directed mutagenesis revealed that while the R177T mutation resulted in an antiporter that was less sensitive to phloretin, the S178T mutation enhanced the inhibitory effect of phloretin on HsNHA2. Our data corroborate the transport properties of HsNHA2 and its interactions with an inhibitor and can be helpful for the development of new therapeutics targeting this antiporter and its pleiotropic physiological functions.
Permanent Link: https://hdl.handle.net/11104/0365379