6ECI

Structure of the FAD binding protein MSMEG_5243 from Mycobacterium smegmatis

6ECI の概要

• エントリーDOI: 10.2210/pdb6eci/pdb
• 分子名称: Pyridoxamine 5'-phosphate oxidase-related, FMN-binding protein, FLAVIN-ADENINE DINUCLEOTIDE, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: flavin adenine dinucleotide (fad) binding protein, flavin/deazaflavin dependent oxidoreductase (fdor), fad-binding protein
• 由来する生物種: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 307141.42

構造登録者

Ahmed, F.H.,Antoney, J.,Carr, P.D.,Jackson, C.J. (登録日: 2018-08-07, 公開日: 2018-12-26, 最終更新日: 2023-10-11)

主引用文献

Harold, L.K.,Antoney, J.,Ahmed, F.H.,Hards, K.,Carr, P.D.,Rapson, T.,Greening, C.,Jackson, C.J.,Cook, G.M.
FAD-sequestering proteins protect mycobacteria against hypoxic and oxidative stress.
J. Biol. Chem., 294:2903-2912, 2019

PubMed Abstract: The ability to persist in the absence of growth triggered by low oxygen levels is a critical process for the survival of mycobacterial species in many environmental niches. (), a gene of unknown function in , is up-regulated in response to hypoxia and regulated by DosRDosS/DosT, an oxygen- and redox-sensing two-component system that is highly conserved in mycobacteria. In this communication, we demonstrate that MSMEG_5243 is a lavin-uestering protein and henceforth refer to it as Fsq. Using an array of biochemical and structural analyses, we show that Fsq is a member of the diverse superfamily of flavin- and deazaflavin-dependent oxidoreductases (FDORs) and is widely distributed in mycobacterial species. We created a markerless deletion mutant of and demonstrate that is required for cell survival during hypoxia. Using deletion and overexpression, we found that enhances cellular resistance to hydrogen peroxide treatment. The X-ray crystal structure of Fsq, solved to 2.7 Å, revealed a homodimeric organization with FAD bound noncovalently. The Fsq structure also uncovered no potential substrate-binding cavities, as the FAD is fully enclosed, and electrochemical studies indicated that the Fsq:FAD complex is relatively inert and does not share common properties with electron-transfer proteins. Taken together, our results suggest that Fsq reduces the formation of reactive oxygen species (ROS) by sequestering free FAD during recovery from hypoxia, thereby protecting the cofactor from undergoing autoxidation to produce ROS. This finding represents a new paradigm in mycobacterial adaptation to hypoxia.

PubMed: 30567740
DOI: 10.1074/jbc.RA118.006237

実験手法

X-RAY DIFFRACTION (2.69 Å)