Human phosphoserine phosphatase (HPSP) regulates the levels of glycine and D-serine, the putative co-agonists for the glycine site of the NMDA receptor in the brain. Here, we describe the first crystal structures of the HPSP in complexes with the competitive inhibitor 2-amino-3-phosphonopropionic acid (AP3) at 2.5 Å, and the phosphate ion (Pi) and the product uncompetitive inhibitor L-serine (HPSP⅐L-Ser⅐Pi) at 2.8 Å. The complex structures reveal that the open-closed environmental change of the active site, generated by local rearrangement of the ␣-helical bundle domain, is important to substrate recognition and hydrolysis. The maximal extent of this structural rearrangement is shown to be about 13 Å at the L4 loop and about 25°at the helix ␣3. Both the structural change and mutagenesis data suggest that Arg-65 and Glu-29 play an important role in the binding of the substrate. Interestingly, the AP3 binding mode turns out to be significantly different from that of the natural substrate, phospho-L-serine, and the HPSP⅐L-Ser⅐Pi structure provides a structural basis for the feedback control mechanism of serine. These analyses allow us to provide a clear model for the mechanism of HPSP and a framework for structure-based drug development. Phosphoserine phosphatase (PSP)1 is an important enzyme in the phosphorylated pathway of serine biosynthesis, which contributes a major portion of the endogenous L-serine (1, 2). In the mammalian nervous system, D-serine is converted from L-serine by serine racemase (3, 4) and acts as a co-agonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, a major neurotransmitter receptor family (5). NMDA receptors require coactivation at a glycine site where D-serine, present in high levels in the mammalian brain, is three times more potent than glycine (6). Recently, a subset of NMDA receptors has been found to be activated by glycine or D-serine in the absence of glutamate (7). The enzymatic reaction of PSP is Mg 2ϩ -dependent and results in the dephosphorylation of phospho-Lserine with the formation of a phosphoenzyme intermediate, which is subsequently autodephosphorylated. The resulting product, L-serine, is not only a precursor for the biosynthesis of glycine but also an uncompetitive inhibitor for the enzymatic reaction of PSP (8). It may be possible to regulate NMDA activity by using selective inhibitors against serine racemase and/or PSP.The PSP family and P-type ATPases are members of the haloacid dehalogenase-like hydrolase family (9 -11). The crystal structures have been elucidated for several members of the haloacid dehalogenase superfamily: the L-2-haloacid dehalogenases, CheY, P-type ATPase and, recently, Methanococcus jannaschii (MJ) PSP (12-16). Three conserved motifs have been observed in amino acid sequences in members of the haloacid dehalogenase superfamily, and these residues are located in the active pocket. The significance of these motifs was confirmed by an assay of mutants for substrate hydrolysis (17). Other phosphoesters, including phosphothreo...
Soil organic matter (SOM) is an important indicator of soil fertility, health and quality. For proper managements of agricultural fields, a long-term monitoring of changes in SOM contents in field and estimation of national accumulation of SOM are required. In this study, SOM in agricultural fields of paddy and upland systems were investigated from 2013 to 2020 for all administrative provinces of South Korea. Total field area was decreased by 4.8% and 9.1% in 2016 and 2020, respectively, compared to 2013. In paddy field, SOM content was 27.9 g kg -1 in 2013, which was gradually increased by 1.1% in 2020. Despite that SOM content increased at a field scale, national SOM accumulation in paddy fields decreased due to reduced paddy area. In upland fields, SOM content was gradually increased by 6.5% from 2013 to 2020. Though SOM content increased, however, SOM accumulation in the total agricultural field at national scale was not affect due to less area than paddy field area. Therefore, total SOM accumulation was continuously decreased from 69.2 Tg in 2013 to 65.3 Tg in 2020 mainly due to decreasing paddy field area. This study showed that in spite of the SOM increase of both fields, national SOM accumulation is decreased with significantly decreasing total field area. Therefore, it is required to increase SOM accumulation at a field scale through proper management of SOM. In addition, it is also necessary to conserve paddy fields to enlarge agricultural SOM at national scale.
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