5O0T

CRYSTAL STRUCTURE OF TRANS-MEMBRANE DOMAIN OF Cylindrospermum stagnale NADPH-OXIDASE 5 (NOX5)

5O0T の概要

• エントリーDOI: 10.2210/pdb5o0t/pdb
• 分子名称: Putative ferric reductase, SULFATE ION, PROTOPORPHYRIN IX CONTAINING FE, ... (8 entities in total)
• 機能のキーワード: membrane protein, reactive oxygen species, oxidative stress, redox biology
• 由来する生物種: Cylindrospermum stagnale PCC 7417
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26589.68

構造登録者

Magnani, F.,Nenci, S.,Mattevi, A. (登録日: 2017-05-17, 公開日: 2017-06-28, 最終更新日: 2024-05-08)

主引用文献

Magnani, F.,Nenci, S.,Millana Fananas, E.,Ceccon, M.,Romero, E.,Fraaije, M.W.,Mattevi, A.
Crystal structures and atomic model of NADPH oxidase.
Proc. Natl. Acad. Sci. U.S.A., 114:6764-6769, 2017

PubMed Abstract: NADPH oxidases (NOXs) are the only enzymes exclusively dedicated to reactive oxygen species (ROS) generation. Dysregulation of these polytopic membrane proteins impacts the redox signaling cascades that control cell proliferation and death. We describe the atomic crystal structures of the catalytic flavin adenine dinucleotide (FAD)- and heme-binding domains of NOX5. The two domains form the core subunit that is common to all seven members of the NOX family. The domain structures were then docked in silico to provide a generic model for the NOX family. A linear arrangement of cofactors (NADPH, FAD, and two membrane-embedded heme moieties) injects electrons from the intracellular side across the membrane to a specific oxygen-binding cavity on the extracytoplasmic side. The overall spatial organization of critical interactions is revealed between the intracellular loops on the transmembrane domain and the NADPH-oxidizing dehydrogenase domain. In particular, the C terminus functions as a toggle switch, which affects access of the NADPH substrate to the enzyme. The essence of this mechanistic model is that the regulatory cues conformationally gate NADPH-binding, implicitly providing a handle for activating/deactivating the very first step in the redox chain. Such insight provides a framework to the discovery of much needed drugs that selectively target the distinct members of the NOX family and interfere with ROS signaling.

PubMed: 28607049
DOI: 10.1073/pnas.1702293114

実験手法

X-RAY DIFFRACTION (2.05 Å)