6o3p
From Proteopedia
Crystal structure of the catalytic domain of mouse Nudt12 in complex with AMP and 3 Mg2+ ions
Structural highlights
FunctionNUD12_MOUSE Hydrolyzes NAD(P)H to NMNH and AMP (2',5'-ADP), and diadenosine diphosphate to AMP. Has also activity towards NAD(P)(+), ADP-ribose and diadenosine triphosphate. May act to regulate the concentration of peroxisomal nicotinamide nucleotide cofactors required for oxidative metabolism in this organelle (By similarity). Publication Abstract from PubMedWe 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(2+) ions at 1.6 A 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. Structural and mechanistic basis of mammalian Nudt12 RNA deNADding.,Grudzien-Nogalska E, Wu Y, Jiao X, Cui H, Mateyak MK, Hart RP, Tong L, Kiledjian M Nat Chem Biol. 2019 Jun;15(6):575-582. doi: 10.1038/s41589-019-0293-7. Epub 2019 , May 17. PMID:31101919[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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