College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea.
Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Republic of Korea.
Biomolecules. 2024 Aug 9;14(8):981. doi: 10.3390/biom14080981.
Iron is crucial for the metabolism and growth of most prokaryotic cells. The ferric uptake regulator (Fur) protein plays a central role in regulating iron homeostasis and metabolic processes in bacteria. It ensures the proper utilization of iron and the maintenance of cellular functions in response to environmental cues. Fur proteins are composed of an N-terminal DNA-binding domain (DBD) and a C-terminal dimerization domain (DD), typically existing as dimers in solution. Fur proteins have conserved metal-binding sites named S1, S2, and S3. Among them, site S2 serves as a regulatory site, and metal binding at S2 results in conformational changes. Additionally, as a transcriptional regulator, Fur specifically binds to a consensus DNA sequence called the Fur box. To elucidate the structural and functional properties of Fur proteins, various structures of metal- or DNA-bound Fur proteins or apo-Fur proteins have been determined. In this review, we focus on the structural properties of Fur proteins according to their ligand-bound state and the drug development strategies targeting Fur proteins. This information provides valuable insights for drug discovery.
铁对于大多数原核细胞的代谢和生长至关重要。铁摄取调节蛋白（Fur）在调节细菌铁平衡和代谢过程中起着核心作用。它确保了铁的适当利用和细胞功能的维持，以响应环境线索。Fur 蛋白由 N 端 DNA 结合域（DBD）和 C 端二聚化域（DD）组成，通常在溶液中以二聚体形式存在。Fur 蛋白具有保守的金属结合位点，分别命名为 S1、S2 和 S3。其中，S2 位点作为调节位点，S2 处的金属结合导致构象变化。此外，作为转录调节因子，Fur 蛋白特异性结合称为 Fur 盒的保守 DNA 序列。为了阐明 Fur 蛋白的结构和功能特性，已经确定了各种金属或 DNA 结合的 Fur 蛋白或无配体 Fur 蛋白的结构。在这篇综述中，我们根据配体结合状态和针对 Fur 蛋白的药物开发策略，重点介绍 Fur 蛋白的结构特性。这些信息为药物发现提供了有价值的见解。
