6X7V

Crystal Structure of the Human Nudix Hydrolase Nudt16

6X7V の概要

• エントリーDOI: 10.2210/pdb6x7v/pdb
• 関連するPDBエントリー: 6X7U
• 分子名称: U8 snoRNA-decapping enzyme, MANGANESE (II) ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: nudix, hydrolase, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 85299.87

構造登録者

Hamilton, K.,Tong, L. (登録日: 2020-05-30, 公開日: 2020-07-01, 最終更新日: 2023-10-18)

主引用文献

Sharma, S.,Grudzien-Nogalska, E.,Hamilton, K.,Jiao, X.,Yang, J.,Tong, L.,Kiledjian, M.
Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs.
Nucleic Acids Res., 48:6788-6798, 2020

PubMed Abstract: We recently reported the presence of nicotinamide adenine dinucleotide (NAD)-capped RNAs in mammalian cells and a role for DXO and the Nudix hydrolase Nudt12 in decapping NAD-capped RNAs (deNADding) in cells. Analysis of 5'caps has revealed that in addition to NAD, mammalian RNAs also contain other metabolite caps including flavin adenine dinucleotide (FAD) and dephosphoCoA (dpCoA). In the present study we systematically screened all mammalian Nudix proteins for their potential deNADing, FAD cap decapping (deFADding) and dpCoA cap decapping (deCoAping) activity. We demonstrate that Nudt16 is a novel deNADding enzyme in mammalian cells. Additionally, we identified seven Nudix proteins-Nudt2, Nudt7, Nudt8, Nudt12, Nudt15, Nudt16 and Nudt19, to possess deCoAping activity in vitro. Moreover, our screening revealed that both mammalian Nudt2 and Nudt16 hydrolyze FAD-capped RNAs in vitro with Nudt16 regulating levels of FAD-capped RNAs in cells. All decapping activities identified hydrolyze the metabolite cap substrate within the diphosphate linkage. Crystal structure of human Nudt16 in complex with FAD at 2.7 Å resolution provide molecular insights into the binding and metal-coordinated hydrolysis of FAD by Nudt16. In summary, our study identifies novel cellular deNADding and deFADding enzymes and establishes a foundation for the selective functionality of the Nudix decapping enzymes on non-canonical metabolite caps.

PubMed: 32432673
DOI: 10.1093/nar/gkaa402

実験手法

X-RAY DIFFRACTION (2.3 Å)