Plasma membrane H+-ATPase (PMA1) (PMA1)

The fungal plasma membrane H+-ATPase (primarily Pma1p) is an essential P-type ATPase responsible for maintaining the electrochemical gradient across the fungal cell membrane (Serrano, 1989; UniProt P05030). By pumping protons out of the cytoplasm, it establishes a membrane potential and a pH gradient that are vital for the secondary active transport of nutrients such as amino acids and sugars (Monk et al., 1995). Because this pump is critical for fungal growth and survival and lacks a direct human ortholog, it represents a highly attractive target for the development of novel antifungal agents (Perlin et al., 1997). Inhibition of Pma1p leads to rapid intracellular acidification and metabolic collapse, effectively killing the fungal cell (Chan et al., 2017). Current research focuses on identifying small molecules, such as ebselen and certain cinnamic acid derivatives, that selectively bind to the fungal pump over human ion-transporting ATPases to minimize side effects (Nakamura et al., 1997; Billack et al., 2001).

Other names

P-type H+-ATPaseProton-translocating ATPasePma1pFungal proton pumpH+-transporting P-type ATPase

Inhibition of the P-type ATPase enzyme activity, preventing the extrusion of protons from the cytoplasm to the extracellular space. This leads to rapid intracellular acidification, dissipation of the membrane potential, and the subsequent cessation of secondary active transport of essential nutrients (Monk et al., 1995; Chan et al., 2017).