9PGW

Crystal structure of STEAP2 N-domain soaked with NADP+ (second collection)

9PGW の概要

• エントリーDOI: 10.2210/pdb9pgw/pdb
• 分子名称: Metalloreductase STEAP2, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: 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: 21616.13

構造登録者

Shin, I.,Liu, A. (登録日: 2025-07-08, 公開日: 2025-10-29, 最終更新日: 2026-05-13)

主引用文献

Shin, I.,Sun, L.Z.,Liu, A.
Structural and spectroscopic resolution of the NADPH redox state in the STEAP2 cytosolic oxidoreductase domain.
J.Biol.Chem., 301:110822-110822, 2025

PubMed Abstract: The six-transmembrane epithelial antigen of prostate (STEAP) family of membrane proteins comprises four human metalloreductases essential for iron and copper homeostasis, redox balance, and cell proliferation. These enzymes transfer electrons from cytosolic NADPH to extracellular ferric and cupric ions via a FAD and heme-dependent pathway. STEAP2, 3, and four contain an N-terminal cytosolic oxidoreductase domain (OxRD) that enables electron input from NADPH, making STEAP2 ideal for studying redox-state cofactor or cosubstrate dynamics. While recent structures of STEAP proteins have been crucial, the redox state of bound NADPH has remained ambiguous in structural data, limiting mechanistic understanding. Here, we address this key missing piece of ambiguity for understanding the electron transfer pathway. We report high-resolution crystal structures of the STEAP2 OxRD with NADPH, in which the redox state of the cosubstrate is directly validated by single-crystal spectroscopy. Comparison with a recent cryoEM structure reveals conformational differences in the FAD-binding region, suggesting a plausible model in which domain reorientation between the N-terminal OxRD and C-terminal transmembrane domain (TMD) facilitates FADH loading and FAD release. These findings resolve a key ambiguity in STEAP structural biology and underscore the importance of experimental redox-state verification in structural studies of redox enzymes.

PubMed: 41101505
DOI: 10.1016/j.jbc.2025.110822

実験手法

X-RAY DIFFRACTION (1.46 Å)