Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Seongjin, Chang, Jeong Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785034605389152256
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