Plasma membrane H+-ATPase (Pma1p) (Pma1p)

The Saccharomyces cerevisiae H+-ATPase, primarily the Pma1p isoform, is an essential P-type ATPase that serves as the major proton pump in the yeast plasma membrane (UniProt P05030). It utilizes the energy from ATP hydrolysis to export protons from the cytoplasm to the extracellular space, a process vital for maintaining intracellular pH homeostasis and generating a large electrochemical gradient across the membrane (Serrano et al., 1986, Nature). This proton motive force is the primary driver for the secondary active transport of essential nutrients, including amino acids and sugars, into the cell (Perlin et al., 1997, J. Biol. Chem.). Because Pma1p is essential for fungal viability and lacks a direct structural ortholog in the human plasma membrane, it is a highly attractive target for the development of novel antifungal therapeutics (Monk et al., 1995, Antimicrob. Agents Chemother.). Pharmacological inhibition of this enzyme by compounds such as ebselen or certain proton pump inhibitors leads to rapid cytosolic acidification, dissipation of the membrane potential, and subsequent growth arrest or cell death (Chan et al., 2007, J. Biol. Chem.). Research into this target is particularly relevant for addressing drug-resistant fungal pathogens like Candida species, which utilize similar H+-ATPase mechanisms for survival and virulence.

Other names

PMA1Proton-exporting ATPaseP-type ATPaseH(+)-transporting ATPaseYGL008CAdenosine triphosphatase

Inhibition of ATP-dependent proton extrusion leading to intracellular acidification and loss of the electrochemical gradient.