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Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95
Human serine racemase (hSR) is a pyridoxal-5′-phosphate (PLP)-dependent dimer that catalyzes the formation of D-serine from L-serine, as well as the dehydration of both L- and D-serine to pyruvate and ammonia. As D-serine is a co-agonist of N-methyl-D-aspartate receptors (NMDARs), hSR is a key enzym...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105370/ https://www.ncbi.nlm.nih.gov/pubmed/35563349 http://dx.doi.org/10.3390/ijms23094959 |
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author | Giaccari, Roberta Marchesani, Francesco Compari, Carlotta Fisicaro, Emilia Mozzarelli, Andrea Campanini, Barbara Bettati, Stefano Bruno, Stefano Faggiano, Serena |
author_facet | Giaccari, Roberta Marchesani, Francesco Compari, Carlotta Fisicaro, Emilia Mozzarelli, Andrea Campanini, Barbara Bettati, Stefano Bruno, Stefano Faggiano, Serena |
author_sort | Giaccari, Roberta |
collection | PubMed |
description | Human serine racemase (hSR) is a pyridoxal-5′-phosphate (PLP)-dependent dimer that catalyzes the formation of D-serine from L-serine, as well as the dehydration of both L- and D-serine to pyruvate and ammonia. As D-serine is a co-agonist of N-methyl-D-aspartate receptors (NMDARs), hSR is a key enzyme in glutamatergic neurotransmission. hSR activity is finely regulated by Mg(2+), ATP, post-translational modifications, and the interaction with protein partners. In particular, the C-terminus of murine SR binds the third PDZ domain (PDZ3) of postsynaptic density protein 95 (PSD-95), a member of the membrane-associated guanylate kinase (MAGUK) family involved in the trafficking and localization of glutamate receptors. The structural details of the interaction and the stability of the complex have not been elucidated yet. We evaluated the binding of recombinant human PSD-95 PDZ3 to hSR by glutaraldehyde cross-linking, pull-down assays, isothermal titration calorimetry, nuclear magnetic resonance, and enzymatic assays. Overall, a weak interaction was observed, confirming the binding for the human orthologs but supporting the hypothesis that a third protein partner (i.e., stargazin) is required for the regulation of hSR activity by PSD-95 and to stabilize their interaction. |
format | Online Article Text |
id | pubmed-9105370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91053702022-05-14 Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95 Giaccari, Roberta Marchesani, Francesco Compari, Carlotta Fisicaro, Emilia Mozzarelli, Andrea Campanini, Barbara Bettati, Stefano Bruno, Stefano Faggiano, Serena Int J Mol Sci Article Human serine racemase (hSR) is a pyridoxal-5′-phosphate (PLP)-dependent dimer that catalyzes the formation of D-serine from L-serine, as well as the dehydration of both L- and D-serine to pyruvate and ammonia. As D-serine is a co-agonist of N-methyl-D-aspartate receptors (NMDARs), hSR is a key enzyme in glutamatergic neurotransmission. hSR activity is finely regulated by Mg(2+), ATP, post-translational modifications, and the interaction with protein partners. In particular, the C-terminus of murine SR binds the third PDZ domain (PDZ3) of postsynaptic density protein 95 (PSD-95), a member of the membrane-associated guanylate kinase (MAGUK) family involved in the trafficking and localization of glutamate receptors. The structural details of the interaction and the stability of the complex have not been elucidated yet. We evaluated the binding of recombinant human PSD-95 PDZ3 to hSR by glutaraldehyde cross-linking, pull-down assays, isothermal titration calorimetry, nuclear magnetic resonance, and enzymatic assays. Overall, a weak interaction was observed, confirming the binding for the human orthologs but supporting the hypothesis that a third protein partner (i.e., stargazin) is required for the regulation of hSR activity by PSD-95 and to stabilize their interaction. MDPI 2022-04-29 /pmc/articles/PMC9105370/ /pubmed/35563349 http://dx.doi.org/10.3390/ijms23094959 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Giaccari, Roberta Marchesani, Francesco Compari, Carlotta Fisicaro, Emilia Mozzarelli, Andrea Campanini, Barbara Bettati, Stefano Bruno, Stefano Faggiano, Serena Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95 |
title | Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95 |
title_full | Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95 |
title_fullStr | Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95 |
title_full_unstemmed | Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95 |
title_short | Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95 |
title_sort | human serine racemase weakly binds the third pdz domain of psd-95 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105370/ https://www.ncbi.nlm.nih.gov/pubmed/35563349 http://dx.doi.org/10.3390/ijms23094959 |
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