9IYK

Crystal structure of hSOD1 in C121 space group

9IYK の概要

• エントリーDOI: 10.2210/pdb9iyk/pdb
• 分子名称: Superoxide dismutase [Cu-Zn], COPPER (II) ION, ZINC ION, ... (6 entities in total)
• 機能のキーワード: hsod1, sod1, superoxide dismutase (cu-zn), oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 196441.08

構造登録者

Yapici, I.,DeMirci, H. (登録日: 2024-07-30, 公開日: 2024-08-14, 最終更新日: 2025-05-28)

主引用文献

Yapici, I.,Tokur, A.G.,Sever, B.,Ciftci, H.,Basak, A.N.,DeMirci, H.
Structural Insights into the Dynamics of Water in SOD1 Catalysis and Drug Interactions.
Int J Mol Sci, 26:-, 2025

PubMed Abstract: Superoxide dismutase 1 (SOD1) is a crucial enzyme that protects cells from oxidative damage by converting superoxide radicals into HO and O. This detoxification process, essential for cellular homeostasis, relies on a precisely orchestrated catalytic mechanism involving the copper cation, while the zinc cation contributes to the structural integrity of the enzyme. This study presents the 2.3 Å crystal structure of human SOD1 (PDB ID: 9IYK), revealing an assembly of six homodimers and twelve distinct active sites. The water molecules form a complex hydrogen-bonding network that drives proton transfer and sustains active site dynamics. Our structure also uncovers subtle conformational changes that highlight the intrinsic flexibility of SOD1, which is essential for its function. Additionally, we observe how these dynamic structural features may be linked to pathological mutations associated with amyotrophic lateral sclerosis (ALS). By advancing our understanding of hSOD1's mechanistic intricacies and the influence of water coordination, this study offers valuable insights for developing therapeutic strategies targeting ALS. Our structure's unique conformations and active site interactions illuminate new facets of hSOD1 function, underscoring the critical role of structural dynamics in enzyme catalysis. Moreover, we conducted a molecular docking analysis using SOD1 for potential radical scavengers and Abelson non-receptor tyrosine kinase (c-Abl, Abl1) inhibitors targeting misfolded SOD1 aggregation along with oxidative stress and apoptosis, respectively. The results showed that CHEMBL1075867, a free radical scavenger derivative, showed the most promising docking results and interactions at the binding site of hSOD1, highlighting its promising role for further studies against SOD1-mediated ALS.

PubMed: 40362464
DOI: 10.3390/ijms26094228

実験手法

X-RAY DIFFRACTION (2.34 Å)