Phosphoserine phosphatase

Figure 10.9 Active site of Methanococcus phosphoserine phosphatase with Mg2+ and phosphoserine in the active site (a) and of human phosphoserine phosphatase with Ca2+ bound and the modelled substrate in the active site (b). (From Peeraer et al., 2004. Reproduced with permission of Blackwell Publishing Ltd.)...

Peeraer, Y., Rabijns, A., Collet, J.-F., Van Scafdngen, E. and De Ranter, C. (2004) How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase, Eur. J. Biochem., 271, 3421-3427. 

D. Serine is synthesized from glucose. The pathway branches from glycolysis at phospho-glyceric acid, which is reduced, transaminated, and dephosphoiylated by phosphoserine phosphatase. Pyruvate kinase is a glycolytic enzyme that functions beyond the branch point for serine synthesis. 

Serine is synthesized in a direct pathway from glycerate-3-phosphate that involves dehydrogenation, transamination, and hydrolysis by a phosphatase (Figure 14.6). Cellular serine concentration controls the pathway through feedback inhibition of phosphoglycerate dehydrogenase and phosphoserine phosphatase. The latter enzyme catalyzes the only irreversible step in the pathway. 

In the biosynthesis of serine from glucose, 3-phosphoglycerate is first oxidized to a 2-keto compound (3-phosphohydroxypyruvate), which is then transaminated to form phosphoserine (Fig. 39.5). Phosphoserine phosphatase removes the phosphate, forming serine. The major sites of serine synthesis are the liver and kidney. 

Regulatory mechanisms maintain serine levels in the body. When serine levels fall, serine synthesis is increased by induction of 3-phosphoglycerate dehydrogenase and by release of the feedback inhibition of phosphoserine phosphatase (caused by higher levels of serine). When serine levels rise, synthesis of serine decreases because synthesis of the dehydrogenase is repressed and the phosphatase is inhibited (see Fig. 39.5). 

Patte, J.C. Clepet, C. Bally, M. Borne, R Mejean, V Foglino, M. ThrH, a homoserine kinase isozyme with in vivo phosphoserine phosphatase activity in Pseudomonas aeruginosa. Microbiology, 145, 845-853 (1999)... 

Residue type and sequential assignments obtained from specifically labeled samples, when combined with 3D heteronuclear data, can significantly increase the efficiency and accuracy of the assignment process, the first step in structure determination by NMR. A protocol for the design of specifically labeled samples with high information content has been developed by Shi et aV. In vitro protein synthesis methods were used to produce four specifically labeled samples of the 23.5 kDa protein phosphoserine phosphatase (PSP) from Methanoccous jannas-chii. Each sample contained two C/ N-labeled amino acids and one N-... 

Fig. 1. Main routes involved in the synthesis and interconversion of glycine and serine in plants. The various steps are numbered, and the necessary enzymes are as follows 1, glycolate oxidase, E.C. 1.1.3.1 2, aminotransferases, serine, E.C. 2.6.1.45, and glutamate, E.C. 2.6.1.4, glyoxylate aminotransferases 3, enzyme complex in mitochondria (see Fig. 2) 4, serine-glyoxylate aminotransferase, E.C. 2.6.1.45 5, glycerate dehydrogenase, E.C. 1.1.1.29 6, glycerate kinase E.C. 2.7.1.31 7, D-3-phosphoglycerate phosphatase, E.C. 3.1.3.38 8, d-3-phosphoglycerate dehydrogenase, E.C. 1.1.1.95 9, phosphoserine aminotransferase, E.C. 2.6.1.52 10, phosphoserine phosphatase, E.C. 3.1.3.3 11, serine hydroxymethyltransferase E.C. 2.1.2.1 12, nonenzymatic decarboxylation 13, formyl tetrahydrofolate synthetase, E.C. 6.3.4.3 14, isocitrate iyase, E.C. 4.1.3.1.

Hanford and Davies (1958) showed that a partly purilied extract from pea epicotyls converted phosphoglycerate to phosphoserine. The reaction was dependent on NAD, glutamate, and pyridoxal phosphate. The first step was presumably catalyzed by phosphoglycerate dehydrogenase and the second by glutamate phosphohydroxypyruvate aminotransferase. Such a phosphoserine aminotransferase was present in extracts of pea seeds, leaves, and apical meristems (Cheung et al., 1968). Little is known of phosphoserine phosphatase in plants, but its presence in spinach leaves is reported by Larsson and Albertsson (1979). 

Phosphoglycerate dehydrogenase 2 phosphoserine aminotransferase 3 phosphoserine phosphatase 4 serine hydroxymethyltransferase 5 glycine aminotransferase 6 phosphoglyceromutase, enolase, pyruvate kinase (Fig. 44) 7 alanine oxoacid aminotransferase... 

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