L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase.

NMDA receptor neurological disorders phosphorylated pathway phosphoserine aminotransferase tumor progression factor

Journal

Protein science : a publication of the Protein Society
ISSN: 1469-896X
Titre abrégé: Protein Sci
Pays: United States
ID NLM: 9211750

Informations de publication

Date de publication:
04 2023
Historique:
revised: 12 01 2023
received: 04 10 2022
accepted: 23 02 2023
medline: 3 4 2023
pubmed: 1 3 2023
entrez: 28 2 2023
Statut: ppublish

Résumé

Organisms from all kingdoms of life synthesize L-serine (L-Ser) from 3-phosphoglycerate through the phosphorylated pathway, a three-step diversion of glycolysis. Phosphoserine aminotransferase (PSAT) catalyzes the intermediate step, the pyridoxal 5'-phosphate-dependent transamination of 3-phosphohydroxypyruvate and L-glutamate to O-phosphoserine (OPS) and α-ketoglutarate. PSAT is particularly relevant in the central nervous system of mammals because L-Ser is the metabolic precursor of D-serine, cysteine, phospholipids, and nucleotides. Several mutations in the human psat gene have been linked to serine deficiency disorders, characterized by severe neurological symptoms. Furthermore, PSAT is overexpressed in many tumors and this overexpression has been associated with poor clinical outcomes. Here, we report the detailed functional and structural characterization of the recombinant human PSAT. The reaction catalyzed by PSAT is reversible, with an equilibrium constant of about 10, and the enzyme is very efficient, with a k

Identifiants

pubmed: 36851825
doi: 10.1002/pro.4609
pmc: PMC10031235
doi:

Substances chimiques

Phosphoglycerate Dehydrogenase EC 1.1.1.95
phosphoserine aminotransferase EC 2.6.1.52
Serine 452VLY9402
Transaminases EC 2.6.1.-
PSAT1 protein, human EC 2.6.1.52

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e4609

Informations de copyright

© 2023 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.

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Auteurs

Francesco Marchesani (F)

Department of Food and Drug, University of Parma, Parma, Italy.

Erika Zangelmi (E)

Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.

Giulia Murtas (G)

Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.

Elisa Costanzi (E)

Protein Facility, Elettra - Sincrotrone Trieste S.C.p.A, Trieste, Italy.

Raheem Ullah (R)

Protein Facility, Elettra - Sincrotrone Trieste S.C.p.A, Trieste, Italy.

Alessio Peracchi (A)

Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.

Stefano Bruno (S)

Department of Food and Drug, University of Parma, Parma, Italy.

Loredano Pollegioni (L)

Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.

Andrea Mozzarelli (A)

Institute of Biophysics, CNR, Pisa, Italy.

Paola Storici (P)

Protein Facility, Elettra - Sincrotrone Trieste S.C.p.A, Trieste, Italy.

Barbara Campanini (B)

Department of Food and Drug, University of Parma, Parma, Italy.

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Classifications MeSH