8WIK

Crystal structure of human FSP1

8WIK の概要

• エントリーDOI: 10.2210/pdb8wik/pdb
• 分子名称: Ferroptosis suppressor protein 1, 6-HYDROXY-FLAVIN-ADENINE DINUCLEOTIDE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: fsp1, ferroptosis, fad, nadh, inhibitor, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42038.57

構造登録者

Feng, S.,Huang, X.,Tang, D.,Qi, S. (登録日: 2023-09-24, 公開日: 2024-05-08)

主引用文献

Feng, S.,Huang, X.,Tang, D.,Liu, X.,Ouyang, L.,Yang, D.,Wang, K.,Liao, B.,Qi, S.
The crystal structure of human ferroptosis suppressive protein 1 in complex with flavin adenine dinucleotide and nicotinamide adenine nucleotide.
MedComm (2020), 5:e479-e479, 2024

PubMed Abstract: Ferroptosis is a recently discovered form of regulated cell death characterized by its distinct dependence on iron and the peroxidation of lipids within cellular membranes. Ferroptosis plays a crucial role in physiological and pathological situations and has attracted the attention of numerous scientists. Ferroptosis suppressive protein 1 (FSP1) is one of the main regulators that negatively regulates ferroptosis through the GPX4-independent FSP1-CoQ10-NAD(P)H axis and is a potential therapeutic target for ferroptosis-related diseases. However, the crystal structure of FSP1 has not been resolved, which hinders the development of therapeutic strategies targeting FSP1. To unravel this puzzle, we purified the human FSP1 (hFSP1) protein using the baculovirus eukaryotic cell expression system and solved its crystal structure at a resolution of 1.75 Å. Furthermore, we evaluated the oxidoreductase activity of hFSP1 with NADH as the substrate and identified E156 as the key amino acid in maintaining hFSP1 activity. Interestingly, our results indicated that hFSP1 exists and functions in a monomeric state. Mutagenesis analysis revealed the critical role of the C-terminal domain in the binding of substrate. These findings significantly enhance our understanding of the functional mechanism of FSP1 and provide a precise model for further drug development.

PubMed: 38414669
DOI: 10.1002/mco2.479

実験手法

X-RAY DIFFRACTION (2 Å)