Archives

  • 2018-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • Because of the formation of phosphoenzyme intermediates the

    2023-01-24

    Because of the formation of phosphoenzyme intermediates, the enzymatic I-BET-762 of P-ATPases can be divided into steps that include a kinase activity, by which an aspartate residue on the enzyme is phosphorylated, and a phosphatase activity, by which the phosphoenzyme is dephosphorylated. Another common feature of these ATPases is their inhibition by submicromolar concentrations of vanadate, acting as a tightly binding phosphate analog (Cantley et al., 1977, Faller et al., 1983, O’Neal et al., 1979). The informative database website “http://traplabs.dk/patbase/ classifies P-ATPases that will not be discussed here; however no insect sequences is present it this database. P-ATPase-encoding genes are found in all five kingdoms of life, but they are more widespread in eukaryotes than in bacteria and archea. Axelsen and Palmgren (1998) divided members of P-ATPase family into 5 branches based on sequence homology, referred to as types I-V. Yet, the simplest and presumably most ancient ion pumps (type-I) are mainly found in bacteria, e.g. the Kdp K+ pump from Escherichia coli (Axelsen and Palmgren, 1998). There is a brief summary of the different substrates which are transported by various members. The type-IB transporters have the physiologically important function of removing toxic ions from the cell (Bull et al., 1993, Tanzi et al., 1993). The most exceptional substrates are transported by type-IV ATPases that are uniquely found in eukaryotes. They catalyze the movement of the amino phospholipids PS, PE or PC from the extracellular to the cytoplasmic leaflet of the plasma membrane lipid bilayer (Poulsen et al., 2008). Although it has not been proven that type-IV ATPases are actually translocating the cationic phospholipids themselves, it has been suggested that they may possibly generate a concentration gradient that subsequently drives phospholipid translocation through another unidentified symporter by transporting other cations (Kühlbrandt, 2004). Not much is known about type V P-ATPases (Table 1). Although it is expected that, like most other P-ATPases, they are cation pumps, their substrate specificity is not established with certainty (Axelsen and Palmgren, 1998, Schultheis et al., 2004). At the cellular level, type V P-ATPases were mostly studied in Saccharomyces cerevisiae. In this organism, there are 16 P-ATPases (Catty et al., 1997). Over 60 P-ATPases from various species have been fully sequenced, and have found to share a number of functional and structural features (Fagan and Saier, 1994). Eukaryotic P-ATPases consist of Na+/K+-ATPases of the plasma membrane of multicellular animals, the gastric and colon H+/K+-ATPases of mammals, the plasma membrane and sarcoplasmic reticulum Ca2+-ATPases, and the plasma membrane H+-ATPases of plants, fungi and lower eukaryotes (Pedersen and Carafoli, 1987, Zhao et al., 1991). The primary structure analysis of P-ATPases showed Most P-ATPases are composed of one polypeptide chain, but H+/K+-ATPase is composed of two subunits, α (114kDa) and β (33kDa) (Toh et al., 1990). Also, their primary structure is generally recognized by conserved sequence motifs in the cytoplasmic domains (Toyoshima et al., 2000). Moreover the structural analysis of this enzyme revealed that all P-ATPases have a simple structure compared with other ion-motive ATPase classes. The single catalytic subunit (named the ‘α-subunit’ in Na+/K+-ATPase) is about 100kDa, with regions that are highly conserved among all P-ATPases, particularly at the hydrophilic and cytoplasmic site for ATP binding and phosphorylation (Fagan and Saier, 1994, Green and Stokes, 1992). Analysis of amino acid sequences revealed all P-type catalytic subunits have the same topological and domain organization. Multiple transmembrane parts exist within both the N-terminal third and C-terminal third of the peptide. In the middle of the peptide, there is a large cytoplasmic domain which contains the nucleotide binding and phosphorylation sites. Some disagreement remains as to the exact location, and even the number, of transmembrane segments (Inesi and Kirtley, 1992). X-ray structures of eukaryotic Ca2+, Na+, K+ and H+ ATPases have been described (Morth et al., 2007, Olesen et al., 2007, Pedersen et al., 2007, Toyoshima et al., 2000); and mechanistic analyses have been presented (Berman, 2001, Gadsby, 2007, Hatori et al., 2007, Kühlbrandt, 2004, Martin, 2005, Møller et al., 2005, Pedersen et al., 2007), leading to well-substantiated mechanistic postulates. Møller et al., 1996, Møller et al., 2005 have analyzed the three cytoplasmic domains. Phylogenetic analysis of ATPases established a common ancestry for all P-ATPases (Fagan and Saier, 1994).