ATPase, P-type

Tlie Na+/K+-ATPase belongs to the P-type ATPases, a family of more than 50 enzymes that also includes the Ca2+-ATPase of the sarcoplasmic reticulum or the gastric H+/K+-ATPase. P-Type ATPases have in common that during ion transport an aspartyl phos-phointermediate is formed by transfer of the y-phosphate group of ATP to the highly conserved sequence DKTGS/T [1]. 

P450 Mono-oxygenase System P-type ATPase(s)... 

Menkes Disease Is Due to Mutations in the Gene Encoding a Copper-Binding P-Type ATPase... 

The cause of Wilson disease was also revealed in 1993, when it was reported that a variety of mutations in a gene encoding a copper-binding P-type ATPase were responsible. The gene is estimated to encode a protein of 1411 amino acids, which is highly homologous to the product of the gene affected in Menkes disease. In a manner not yet fully explained, a nonfunctional ATPase causes defective excretion of copper into the bile, a reduction of incorporation of copper into... 

Ceruloplasmin contains substantial amounts of copper, but albumin appears to be more important with regard to its transport. Both Wilson disease and Menkes disease, which reflect abnormahties of copper metabohsm, have been found to be due to mutations in genes encoding copper-binding P-type ATPases. 

Information about the putative folding of the H,K-ATPase catalytic subunit through the membrane has been obtained by the combined use of hydropathy analysis according to the criteria of Kyte and Doolittle [51], identification of sites sensitive to chemical modification [46,48,50,52-55], and localization of epitopes of monoclonal antibodies [56]. The model of the H,K-ATPase catalytic subunit (Fig. 1) which has emerged from these studies shows ten transmembrane segments and contains cytosolic N- and C-termini [53]. This secondary structure of the catalytic subunit is probably a common feature of the catalytic subunits of P-type ATPases, since evidence supporting a ten a-helical model with cytosolic N- and C-termini has also been published recently for both Ca-ATPase of the sarcoplasmic reticulum and Na,K-ATPase [57-59]. 

Hydropathy analysis predicted that there are four major transmembrane domains (M1-M4) prior to the phosphorylation site at Asp . The existence of these four transmembrane segments in the N-terminal half of the catalytic subunit is generally accepted for all P-type ATPases. The four transmembrane sequences are followed by a large cytosolic loop that contains the phosphorylation site Asp, the pyridoxal... 

The widely accepted model, of how the class of P-type ATPases transports ions... 

Weissman Z, I Berdicevsky, BZ Cavari, D Kornotzer (2000) The high copper tolerance of Candida albicans is mediated by a P-type ATPase. Proc Natl Acad Sci USA 97 3520-3525... 

Rensing, C., Mitra, B., and Rosen, B.P., The zntA gene of Escherichia coli encodes aZn(II)-translocating P-type ATPase, Proc Natl Acad Sci USA, 94 (26), 14326-14331, 1997. 

Figure 7.31 Schematic structures for Menkes and Wilson disease copper-transporting P type ATPases. (Adapted with permission from Figure 2 of Sarkar, B. Chem. Rev., 1999, 99(9), 2535-2544. Copyright 1999, American Chemical Society.)...

P-type ATPases from eukaryotes, bacteria, and Archaea catalyse cation uptake and/or efflux driven by ATP hydrolysis. Bacterial P-type ATPases... 

Mammalian cells maintain a lower concentration of Na+ (around 12 mM) and a higher concentration of K+ (around 140 mM) than in the surrounding extracellular medium (respectively, 145 and 4 mM). The system (Na+-K+)-ATPase, which maintains high intracellular K+ and low intracellular Na+, is localized in the plasma membrane, and belongs to the family of P-type ATPases. Other members of the family in eukaryotes are the sarcoplasmic reticulum and plasma membrane Ca2+ ATPases and, in plants, the H+-ATPases. The overall reaction catalysed is ... 

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