6O3P

Crystal structure of the catalytic domain of mouse Nudt12 in complex with AMP and 3 Mg2+ ions

Summary for 6O3P

• Entry DOI: 10.2210/pdb6o3p/pdb
• Descriptor: Peroxisomal NADH pyrophosphatase NUDT12, ADENOSINE MONOPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: nudix protein, denadding enzyme, complex, hydrolase
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 76449.61

Authors

Tong, L.,Wu, Y. (deposition date: 2019-02-27, release date: 2019-05-29, Last modification date: 2023-10-11)

Primary citation

Grudzien-Nogalska, E.,Wu, Y.,Jiao, X.,Cui, H.,Mateyak, M.K.,Hart, R.P.,Tong, L.,Kiledjian, M.
Structural and mechanistic basis of mammalian Nudt12 RNA deNADding.
Nat.Chem.Biol., 15:575-582, 2019

PubMed Abstract: We recently demonstrated that mammalian cells harbor nicotinamide adenine dinucleotide (NAD)-capped messenger RNAs that are hydrolyzed by the DXO deNADding enzyme. Here, we report that the Nudix protein Nudt12 is a second mammalian deNADding enzyme structurally and mechanistically distinct from DXO and targeting different RNAs. The crystal structure of mouse Nudt12 in complex with the deNADding product AMP and three Mg ions at 1.6 Å resolution provides insights into the molecular basis of the deNADding activity in the NAD pyrophosphate. Disruption of the Nudt12 gene stabilizes transfected NAD-capped RNA in cells, and its endogenous NAD-capped mRNA targets are enriched in those encoding proteins involved in cellular energetics. Furthermore, exposure of cells to nutrient or environmental stress manifests changes in NAD-capped RNA levels that are selectively responsive to Nudt12 or DXO, respectively, indicating an association of deNADding to cellular metabolism.

PubMed: 31101919
DOI: 10.1038/s41589-019-0293-7

Experimental method

X-RAY DIFFRACTION (1.6 Å)