P-type ATPases as drug targets: tools for medicine and science.
P-type ATPases catalyze the selective active transport of ions like H+, Na+, K+, Ca2+, Zn2+, and Cu2+ across diverse biological membrane systems. Many members of the P-type ATPase protein family, such as the Na+,K+-, H+,K+-, Ca2+-, and H+-ATPases, are involved in the development of pathophysiological conditions or provide critical function to pathogens. Therefore, they seem to be promising targets for future drugs and novel antifungal agents and herbicides. Here, we review the current knowledge about P-type ATPase inhibitors and their present use as tools in science, medicine, and biotechnology. Recent structural information on a variety of P-type ATPase family members signifies that all P-type ATPases can be expected to share a similar basic structure and a similar basic machinery of ion transport. The ion transport pathway crossing the membrane lipid bilayer is constructed of two access channels leading from either side of the membrane to the ion binding sites at a central cavity. The selective opening and closure of the access channels allows vectorial access/release of ions from the binding sites. Recent structural information along with new homology modeling of diverse P-type ATPases in complex with known ligands demonstrate that the most proficient way for the development of efficient and selective drugs is to target their ion transport pathway.
Yatime
Laure
L
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Denmark.
Buch-Pedersen
Morten J
MJ
Musgaard
Maria
M
Morth
J Preben
JP
Lund Winther
Anne-Marie
AM
Pedersen
Bjørn P
BP
Olesen
Claus
C
Andersen
Jens Peter
JP
Vilsen
Bente
B
Schiøtt
Birgit
B
Palmgren
Michael G
MG
Møller
Jesper V
JV
Nissen
Poul
P
Fedosova
Natalya
N
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D006801:Humans; D008511:Medicine; D008958:Models, Molecular; D004364:Pharmaceutical Preparations; D054328:Proton Pump Inhibitors; D017494:Proton Pumps / Q000737:chemistry; D012586:Science
D004364:Pharmaceutical Preparations; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D000251:Adenosine Triphosphatases