4.6 Article

Structural Analysis of Spermidine Synthase from Kluyveromyces lactis

Journal

MOLECULES
Volume 28, Issue 8, Pages -

Publisher

MDPI
DOI: 10.3390/molecules28083446

Keywords

SpdS; spermidine; putrescine; polyamine; aminopropyltransferase

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Spermidine is a polyamine molecule that performs various cellular functions and is generated from putrescine by spermidine synthase (SpdS). Although the molecular mechanism of SpdS function has been well-established, its structure-based evolutionary relationships remain to be fully understood. This study determined the crystal structure of an apo-form of SpdS from Kluyveromyces lactis (KlSpdS) and identified a conformational change that provides insights into the structural diversity of SpdS in fungal species.
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 angstrom resolution. Structural comparison with its homologs revealed a conformational change in the alpha 6 helix linked to the gate-keeping loop, with approximately 40 degrees 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.

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