scholarly journals 3-phosphoserine phosphatase deficiency

2020 ◽  
Author(s):  
Keyword(s):  
Phosphoserine Phosphatase

Differential effects of diabetes on adipocyte and liver phosphotyrosine and phosphoserine phosphatase activities

Diabetes ◽  
1991 ◽  
Vol 40 (12) ◽  
pp. 1620-1629 ◽  
Author(s):  
N. Begum ◽  
K. E. Sussman ◽  
B. Draznin
Keyword(s):  
Phosphatase Activities ◽  
Differential Effects ◽  
Phosphoserine Phosphatase

Crystal structures and snapshots along the reaction pathway of human phosphoserine phosphatase

2019 ◽  
Vol 75 (6) ◽  
pp. 592-604 ◽  
Author(s):  
Marie Haufroid ◽  
Manon Mirgaux ◽  
Laurence Leherte ◽  
Johan Wouters
Keyword(s):  
Molecular Dynamics ◽  
Reaction Mechanism ◽  
Crystal Structures ◽  
Reaction Pathway ◽  
Living Cells ◽  
Homocysteic Acid ◽  
Phosphoserine Phosphatase ◽  
Key Enzyme ◽  
The Subject ◽  
Dynamics Simulations

The equilibrium between phosphorylation and dephosphorylation is one of the most important processes that takes place in living cells. Human phosphoserine phosphatase (hPSP) is a key enzyme in the production of serine by the dephosphorylation of phospho-L-serine. It is directly involved in the biosynthesis of other important metabolites such as glycine and D-serine (a neuromodulator). hPSP is involved in the survival mechanism of cancer cells and has recently been found to be an essential biomarker. Here, three new high-resolution crystal structures of hPSP (1.5–2.0 Å) in complexes with phosphoserine and with serine, which are the substrate and the product of the reaction, respectively, and in complex with a noncleavable substrate analogue (homocysteic acid) are presented. New types of interactions take place between the enzyme and its ligands. Moreover, the loop involved in the open/closed state of the enzyme is fully refined in a totally unfolded conformation. This loop is further studied through molecular-dynamics simulations. Finally, all of these analyses allow a more complete reaction mechanism for this enzyme to be proposed which is consistent with previous publications on the subject.

scholarly journals Erratum to: Novel Report of Phosphoserine Phosphatase Deficiency in an Adult with Myeloneuropathy and Limb Contractures

2014 ◽  
pp. 109-109
Author(s):  
Heather M. Byers ◽  
Robin L. Bennett ◽  
Emily A. Malouf ◽  
Michael D. Weiss ◽  
Jie Feng ◽  
...  
Keyword(s):  
Phosphoserine Phosphatase

scholarly journals Identification and Repurposing of Trisubstituted Harmine Derivatives as Novel Inhibitors of Mycobacterium tuberculosis Phosphoserine Phosphatase

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 415 ◽  
Author(s):  
Elise Pierson ◽  
Marie Haufroid ◽  
Tannu Priya Gosain ◽  
Pankaj Chopra ◽  
Ramandeep Singh ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Metabolic Enzyme ◽  
Phosphoserine Phosphatase ◽  
Cellular Assays ◽  
Promising Target ◽  
Global Health Issue ◽  
Serine Pathway

Mycobacterium tuberculosis is still the deadliest bacterial pathogen worldwide and the increasing number of multidrug-resistant tuberculosis cases further complicates this global health issue. M. tuberculosis phosphoserine phosphatase SerB2 is a promising target for drug design. Besides being a key essential metabolic enzyme of the pathogen’s serine pathway, it appears to be involved in immune evasion mechanisms. In this work, a malachite green-based phosphatase assay has been used to screen 122 compounds from an internal chemolibrary. Trisubstituted harmine derivatives were found among the best hits that inhibited SerB2 activity. Synthesis of an original compound helped to discuss a brief structure activity relationship evaluation. Kinetics experiments showed that the most potent derivatives inhibit the phosphatase in a parabolic competitive fashion with apparent inhibition constants ( K i ) values in the micromolar range. Their interaction modes with the enzyme were investigated through induced fit docking experiments, leading to results consistent with the experimental data. Cellular assays showed that the selected compounds also inhibited M. tuberculosis growth in vitro. Those promising results may provide a basis for the development of new antimycobacterial agents targeting SerB2.

scholarly journals A chromosomal locus encoding a phosphoserine phosphatase- and a truncated MinD-like protein affects differentiation inStreptomyces azureusATCC14921

2000 ◽  
Vol 190 (1) ◽  
pp. 133-139 ◽  
Author(s):  
Takashi Nishiyama ◽  
Hirohito Sakemi ◽  
Harukata Sumi ◽  
Satoko Tokunaga ◽  
Katsumi Doi ◽  
...  
Keyword(s):  
Chromosomal Locus ◽  
Phosphoserine Phosphatase

o-Phosphoserine phosphatase

1958 ◽  
Vol 28 ◽  
pp. 223-224 ◽  
Author(s):  
Francis C. Neuhaus ◽  
William L. Byrne
Keyword(s):  
Phosphoserine Phosphatase

scholarly journals Phosphoserine Phosphatase Is Required for Serine and One-Carbon Unit Synthesis in Hydrogenobacter thermophilus

2017 ◽  
Vol 199 (21) ◽  
Author(s):  
Keugtae Kim ◽  
Yoko Chiba ◽  
Azusa Kobayashi ◽  
Hiroyuki Arai ◽  
Masaharu Ishii
Keyword(s):  
Physiological Role ◽  
Tca Cycle ◽  
Content Type ◽  
Phosphoserine Phosphatase ◽  
Genes Encoding ◽  
Hydrogenobacter Thermophilus ◽  
Glycine Cleavage ◽  
Major Donor ◽  
Serine Biosynthesis

ABSTRACT Hydrogenobacter thermophilus is an obligate chemolithoautotrophic bacterium of the phylum Aquificae and is capable of fixing carbon dioxide through the reductive tricarboxylic acid (TCA) cycle. The recent discovery of two novel-type phosphoserine phosphatases (PSPs) in H. thermophilus suggests the presence of a phosphorylated serine biosynthesis pathway; however, the physiological role of these novel-type metal-independent PSPs (iPSPs) in H. thermophilus has not been confirmed. In the present study, a mutant strain with a deletion of pspA, the catalytic subunit of iPSPs, was constructed and characterized. The generated mutant was a serine auxotroph, suggesting that the novel-type PSPs and phosphorylated serine synthesis pathway are essential for serine anabolism in H. thermophilus. As an autotrophic medium supplemented with glycine did not support the growth of the mutant, the reversible enzyme serine hydroxymethyltransferase does not appear to synthesize serine from glycine and may therefore generate glycine and 5,10-CH2-tetrahydrofolate (5,10-CH2-THF) from serine. This speculation is supported by the lack of glycine cleavage activity, which is needed to generate 5,10-CH2-THF, in H. thermophilus. Determining the mechanism of 5,10-CH2-THF synthesis is important for understanding the fundamental anabolic pathways of organisms, because 5,10-CH2-THF is a major one-carbon donor that is used for the synthesis of various essential compounds, including nucleic and amino acids. The findings from the present experiments using a pspA deletion mutant have confirmed the physiological role of iPSPs as serine producers and show that serine is a major donor of one-carbon units in H. thermophilus. IMPORTANCE Serine biosynthesis and catabolism pathways are intimately related to the metabolism of 5,10-CH2-THF, a one-carbon donor that is utilized for the biosynthesis of various essential compounds. For this reason, determining the mechanism of serine synthesis is important for understanding the fundamental anabolic pathways of microorganisms. In the present study, we experimentally confirmed that a novel phosphoserine phosphatase in the obligate chemolithoautotrophic bacterium Hydrogenobacter thermophilus is essential for serine biosynthesis. This finding indicates that serine is synthesized from an intermediate of gluconeogenesis in H. thermophilus. In addition, because glycine cleavage system activity and genes encoding an enzyme capable of producing 5,10-CH2-THF were not detected, serine appears to be the major one-carbon donor to tetrahydrofolate (THF) in H. thermophilus.

Structural Characterization of the Reaction Pathway in Phosphoserine Phosphatase: Crystallographic “snapshots” of Intermediate States

2002 ◽  
Vol 319 (2) ◽  
pp. 421-431 ◽  
Author(s):  
Weiru Wang ◽  
Ho S. Cho ◽  
Rosalind Kim ◽  
Jaru Jancarik ◽  
Hisao Yokota ◽  
...  
Keyword(s):  
Structural Characterization ◽  
Reaction Pathway ◽  
Phosphoserine Phosphatase ◽  
Intermediate States
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