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Structural Analysis of Spermidine Synthase from Kluyveromyces lactis
Spermidine is a polyamine molecule that performs various cellular functions, such as DNA and RNA stabilization, autophagy modulation, and eIF5A formation, and is generated from putrescine by aminopropyltransferase spermidine synthase (SpdS). During synthesis, the aminopropyl moiety is donated from d...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146546/ https://www.ncbi.nlm.nih.gov/pubmed/37110680 http://dx.doi.org/10.3390/molecules28083446 |
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author | Kim, Seongjin Chang, Jeong Ho |
author_facet | Kim, Seongjin Chang, Jeong Ho |
author_sort | Kim, Seongjin |
collection | PubMed |
description | Spermidine is a polyamine molecule that performs various cellular functions, such as DNA and RNA stabilization, autophagy modulation, and eIF5A formation, and is generated from putrescine by aminopropyltransferase spermidine synthase (SpdS). During synthesis, the aminopropyl moiety is donated from decarboxylated S-adenosylmethionine to form putrescine, with 5′-deoxy-5′-methylthioadenosine being produced as a byproduct. Although the molecular mechanism of SpdS function has been well-established, its structure-based evolutionary relationships remain to be fully understood. Moreover, only a few structural studies have been conducted on SpdS from fungal species. Here, we determined the crystal structure of an apo-form of SpdS from Kluyveromyces lactis (KlSpdS) at 1.9 Å resolution. Structural comparison with its homologs revealed a conformational change in the α6 helix linked to the gate-keeping loop, with approximately 40° outward rotation. This change caused the catalytic residue Asp170 to move outward, possibly due to the absence of a ligand in the active site. These findings improve our understanding of the structural diversity of SpdS and provide a missing link that expands our knowledge of the structural features of SpdS in fungal species. |
format | Online Article Text |
id | pubmed-10146546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101465462023-04-29 Structural Analysis of Spermidine Synthase from Kluyveromyces lactis Kim, Seongjin Chang, Jeong Ho Molecules Article Spermidine is a polyamine molecule that performs various cellular functions, such as DNA and RNA stabilization, autophagy modulation, and eIF5A formation, and is generated from putrescine by aminopropyltransferase spermidine synthase (SpdS). During synthesis, the aminopropyl moiety is donated from decarboxylated S-adenosylmethionine to form putrescine, with 5′-deoxy-5′-methylthioadenosine being produced as a byproduct. Although the molecular mechanism of SpdS function has been well-established, its structure-based evolutionary relationships remain to be fully understood. Moreover, only a few structural studies have been conducted on SpdS from fungal species. Here, we determined the crystal structure of an apo-form of SpdS from Kluyveromyces lactis (KlSpdS) at 1.9 Å resolution. Structural comparison with its homologs revealed a conformational change in the α6 helix linked to the gate-keeping loop, with approximately 40° outward rotation. This change caused the catalytic residue Asp170 to move outward, possibly due to the absence of a ligand in the active site. These findings improve our understanding of the structural diversity of SpdS and provide a missing link that expands our knowledge of the structural features of SpdS in fungal species. MDPI 2023-04-13 /pmc/articles/PMC10146546/ /pubmed/37110680 http://dx.doi.org/10.3390/molecules28083446 Text en © 2023 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 Kim, Seongjin Chang, Jeong Ho Structural Analysis of Spermidine Synthase from Kluyveromyces lactis |
title | Structural Analysis of Spermidine Synthase from Kluyveromyces lactis |
title_full | Structural Analysis of Spermidine Synthase from Kluyveromyces lactis |
title_fullStr | Structural Analysis of Spermidine Synthase from Kluyveromyces lactis |
title_full_unstemmed | Structural Analysis of Spermidine Synthase from Kluyveromyces lactis |
title_short | Structural Analysis of Spermidine Synthase from Kluyveromyces lactis |
title_sort | structural analysis of spermidine synthase from kluyveromyces lactis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146546/ https://www.ncbi.nlm.nih.gov/pubmed/37110680 http://dx.doi.org/10.3390/molecules28083446 |
work_keys_str_mv | AT kimseongjin structuralanalysisofspermidinesynthasefromkluyveromyceslactis AT changjeongho structuralanalysisofspermidinesynthasefromkluyveromyceslactis |