Protein phosphatases subunit structure

The phosphoprotein-ubiquitin ligases hgate ubiquitin exclusively to phosphorylated proteins. In this system, ubiquitination and degradation are controlled by the phosphorylation status of the target proteins, which is in turn dependent on the regulated activity of protein kinases (or protein phosphatases). Phosphorylation of the target proteins often occurs in sequence elements rich in the aminoacids P,E,S, and T (PEST sequences). For target proteins and the subunit structure, see 13.3.1. 

Groves, M. R., Hanlon, N., Turowski, P., Hemmings, B. A., and Barford, D. (1999). The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs. Cell 8, 99-110. 

Egloff MP, Johnson DF, Moorhead G, Cohen PT, Cohen P, Barford D (1997) Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1. Embo J 76 1876-1887. 

In general there are three phosphatase families alkaline, acid, and protein phosphatases. Alkaline phosphatases are typically dimers that contain three metal ions per subunit and have a pH optimum pH above 8. Acid phosphatases exhibit an optimum pH<7 and are usually divided into three classes low molecular weight acid phosphatases (<20 kDa), high molecular weight acid phosphatases (50-60 kDa), and purple acid phosphatases (which contain an Fe-Fe or Fe-Zn center at the active site). Phosphatases specific for I-l-P appear to be most similar (in kinetic characteristics but not in mechanism) to the alkaline phosphatases, but their structures define a superfamily that also includes inositol polyphosphate 1-phosphatase, fructose 1, 6-bisphosphatase, and Hal2. The members of this superfamily share a common structural core of 5 a-helices and 11 (3-strands. Many are Li+-sensitive (York et al., 1995), and more recent structures of archaeal IMPase proteins suggest the Li+ -sensitivity is related to the disposition of a flexible loop near the active site (Stieglitz et al., 2002). 

M. P. Egloff, P. T. Cohen, P. Reinemer, and D. Barford. Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate. Nature, 376 (6543), 745 753, 1995. 

Structure and expression of a 72-kDa regulatory subunit of protein phosphatase 2A. Evidence for different size forms produced by alternative splicing. J Biol Chem 268 15267-15276... 

The crystal structure of the catalytic subunit of mammalian protein phosphatase-1 complexed with microcystin-LR has recently been determined at 2.1 A resolution (139). The metalloenzyme exhibits a fold unrelated to the known structures of catalytic subunits of tyrosine phosphatases. The two metal ions are positioned in a central p-a-P -a-P scaffold at the active site, from which three surface grooves protrude as potential binding sites for substrates and inhibitors. The C-terminus of the catalytic subunit is located at the end of one of these grooves, so that regulatory sequences following this domain may possibly modulate the function. This fold is expected to be closely preserved in the protein phosphatases 2A and 2B. 

Hubbard MJ, Cohen P (1989) The glycogen-binding subunit of protein phosphatase-IG from rabbit skeletal muscle. Further characterisation of its structure and glycogenbinding properties. Eur J Biochem 180 457-465... 

Another human cDNA array study was performed on LPS-stimulated PMN (4h) and revealed 134 genes that were upregulated [121, 122]. These included chemokines, cytokines, signaling molecules and transcriptional regulators. Proteomic analysis revealed upregulation of the proinflammatory molecules annexin 111, leukocyte elastase inhibitor, and the signaling molecules phosphostathmin, protein phosphatase 1 and p-catalytic subunit, as well as structural proteins such as protein tyrosine kinase 9-like, nonmuscle myosin heavy chain and moesin [121]. 

Primary structure analysis of phenylphosphate carboxylase of T. aromatica is performed in detail, to clarify the reaction mechanism involving four kinds of subunits. The a, (3, y, 8 subunits have molecular masses of 54, 53, 18, and lOkDa, respectively, which make up the active phenylphosphate carboxylase. The primary structures of a and (3 subunits show homology with 3-octaprenyl-4-hydroxybenzoate decarboxylase, 4-hydroxybenzoate decarboxylase, and vanil-late decarboxylase, whereas y subunit is unique and not characterized. The 18kDa 8 subunit belongs to a hydratase/phosphatase protein family. Taking 4-hydroxybenzoate decarboxylase into consideration, Schiihle and Fuchs postulate that the a(3y core enzyme catalyzes the reversible carboxylation. ... 

Goldberg, J., Huang, H. B., Kwon,Y. G., Greengard, P., Nairn, A. C. and Kuriyan, J. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 376 745-753,1995. 

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