Department of Biology Education, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea.
Department of Biomedical Convergence Science and Technology, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea.
Molecules. 2023 Apr 13;28(8):3446. doi: 10.3390/molecules28083446.
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 (SpdS) 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.
精胺是一种多胺分子，具有多种细胞功能，如 DNA 和 RNA 稳定、自噬调节和 eIF5A 形成，并由腐胺通过氨基丙基转移酶精胺合酶 (SpdS) 生成。在合成过程中，氨基丙基部分由脱羧 S-腺苷甲硫氨酸提供，形成腐胺，同时产生 5'-脱氧-5'-甲基硫代腺苷作为副产物。尽管 SpdS 功能的分子机制已经得到很好的确立，但它的结构基进化关系仍有待充分理解。此外，只有少数关于真菌物种 SpdS 的结构研究已经开展。在这里，我们确定了 SpdS 的无配体形式的晶体结构，分辨率为 1.9 Å。与同源物的结构比较揭示了与门控环相连的α6 螺旋的构象变化，约向外旋转 40°。这种变化导致催化残基 Asp170 向外移动，可能是由于活性位点中没有配体。这些发现提高了我们对 SpdS 结构多样性的理解，并提供了一个缺失的环节，扩展了我们对真菌物种中 SpdS 结构特征的知识。
