Atpase Research Paper
The fungal plasma membrane proton-ATPase is a membrane protein that belongs to primary ATPase-transporters class. ATPases in this class are characterized by their ability to convert the chemical energy generated by ATP hydrolysis to kinetic energy required for the transport of ions through the membrane. ATPase transporters are classified to P-,F-,V-ATPases and ABC transporters. Fungal plasma membrane proton-ATPase belongs to class P-type ATPases . Other members of the P-type ATPase class include the Na+,K+-ATPases of animal cells, the Ca2+-ATPases of red blood cells, the gastric H+,K+-ATPase, and the sarcoplasmic reticulum, the proton-pumping ATPases of some lower eukaryotic parasites, plant cells, and the ion-specific ATPases of some prokaryotic cells.
Fungal plasma membrane proton pumps actively extrude protons from fungal cells. The pH gradient generated by this process has two major physiological roles:
Firstly, it provides the energy for secondary active transport. This energy drives the transport of three types of nutrients inside the cell, the uncharged molecules (sugars, neutral amino acids) the anionic substrates (chloride, phosphate, sulfate, lactate, acetate and anionic amino acids) and cationic substrates (K+, NH4+, Na+, …show more content…
Ca2+, Mg2+ and cationic amino acids). In addition, the extrusion of undesirable compounds is driven by the proton gradient (Figure 10). Secondly, it regulates both the intracellular and extracellular pH. The internal alkalinisation and external acidification resulting from the ATPase activity mediates the induction of growth by glucose in yeast.31
Figure 10: Representation of fungal plasma membrane ATPase function.
(1) Primary proton pump. (2) Cation (C+) channel. (3) Anion (A-) channel. (4) Proton-symport. (5) Proton-antiport.31
The essential role of fungal plasma membrane proton ATPase in fungal cell shows that it is a promising target for antifungal agents, but the lack of high resolution crystal structure hinders the development of potent inhibitors. They best crystal structure available today is the structure provided by Bjørn P. Pedersen et al. which has 3.8 Å resolution. At this resolution, structure based drug design using computational chemistry cannot be conducted accurately, so ligand based drug design approach, starting from a known ligand must be
employed.
Fungal plasma membrane proton pumps actively extrude protons from fungal cells. The pH gradient generated by this process has two major physiological roles:
Firstly, it provides the energy for secondary active transport. This energy drives the transport of three types of nutrients inside the cell, the uncharged molecules (sugars, neutral amino acids) the anionic substrates (chloride, phosphate, sulfate, lactate, acetate and anionic amino acids) and cationic substrates (K+, NH4+, Na+, …show more content…
Ca2+, Mg2+ and cationic amino acids). In addition, the extrusion of undesirable compounds is driven by the proton gradient (Figure 10). Secondly, it regulates both the intracellular and extracellular pH. The internal alkalinisation and external acidification resulting from the ATPase activity mediates the induction of growth by glucose in yeast.31
Figure 10: Representation of fungal plasma membrane ATPase function.
(1) Primary proton pump. (2) Cation (C+) channel. (3) Anion (A-) channel. (4) Proton-symport. (5) Proton-antiport.31
The essential role of fungal plasma membrane proton ATPase in fungal cell shows that it is a promising target for antifungal agents, but the lack of high resolution crystal structure hinders the development of potent inhibitors. They best crystal structure available today is the structure provided by Bjørn P. Pedersen et al. which has 3.8 Å resolution. At this resolution, structure based drug design using computational chemistry cannot be conducted accurately, so ligand based drug design approach, starting from a known ligand must be
employed.