7UWT

Structure of Oxygen-Insensitive NAD(P)H-dependent Nitroreductase NfsB_Vv F70A/F108Y (NTR 2.0) in complex with FMN at 1.85 Angstroms resolution

7UWT の概要

• エントリーDOI: 10.2210/pdb7uwt/pdb
• 分子名称: Dihydropteridine reductase, FLAVIN MONONUCLEOTIDE, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: nitroreductase, oxidoreductase, flavoenzyme, metronidazole reductase
• 由来する生物種: Vibrio vulnificus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51317.88

構造登録者

Sharrock, A.V.,Arcus, V.,Mumm, J.S.,Ackerley, D.F. (登録日: 2022-05-03, 公開日: 2022-05-18, 最終更新日: 2023-10-25)

主引用文献

Sharrock, A.V.,Mumm, J.S.,Bagdziunas, G.,Cenas, N.,Arcus, V.L.,Ackerley, D.F.
The Crystal Structure of Engineered Nitroreductase NTR 2.0 and Impact of F70A and F108Y Substitutions on Substrate Specificity.
Int J Mol Sci, 24:-, 2023

PubMed Abstract: Bacterial nitroreductase enzymes that convert prodrugs to cytotoxins are valuable tools for creating transgenic targeted ablation models to study cellular function and cell-specific regeneration paradigms. We recently engineered a nitroreductase ("NTR 2.0") for substantially enhanced reduction of the prodrug metronidazole, which permits faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms useful for modelling chronic diseases. To provide insight into the enhanced enzymatic mechanism of NTR 2.0, we have solved the X-ray crystal structure at 1.85 Angstroms resolution and compared it to the parental enzyme, NfsB from . We additionally present a survey of reductive activity with eight alternative nitroaromatic substrates, to provide access to alternative ablation prodrugs, and explore applications such as remediation of dinitrotoluene pollutants. The predicted binding modes of four key substrates were investigated using molecular modelling.

PubMed: 37047605
DOI: 10.3390/ijms24076633

実験手法

X-RAY DIFFRACTION (1.85 Å)