6X7U

Crystal Structure of the Human Nudix Hydrolase Nudt16 in complex with FAD

Summary for 6X7U

• Entry DOI: 10.2210/pdb6x7u/pdb
• Descriptor: U8 snoRNA-decapping enzyme, FLAVIN-ADENINE DINUCLEOTIDE, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: nudix, hydrolase, fad, decapping, rna binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 41668.56

Authors

Hamilton, K.,Tong, L. (deposition date: 2020-05-30, release date: 2020-07-01, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)