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Human Nudix motif 16 (NUDT16)

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PDB Code 3COU Target Class Nucleotide metabolism Target NUDT16 Alias FLJ31265, NUDT16 Disease Area/Function cancer Date Deposited Mar 29 2008 Authors L.TRESAUGUES, M.MOCHE, C.H.ARROWSMITH, H.BERGLUND, R.D.BUSAM, R.COLLINS, L.G.DAHLGREN, A.EDWARDS, S.FLODIN, A.FLORES, S.GRASLUND, M.HAMMARSTROM, A.JOHANSSON, I.JOHANSSON, A.KALLAS, T, KARLBERG, T.KOTENYOVA, L.LEHTIO, M.E.NILSSON, T.NYMAN, C.PERSSON, J.SAGEMARK, H.SCHUELER, L.SVENSSON, A.G.THORSELL, S.VAN DEN BERG, M.WELIN, J.WEIGELT, M.WIKSTROM, P.NORDLUND

About this structure

NUDT16 is a 195 aminoacid long protein which belongs to the Nudix hydrolase superfamily [1]. The activities of these enzymes are targeted against a broad range of substrate containing a nucleoside diphosphate linked to another moiety (NDP-X) leading to NMP + P-X. NUDT16 has a “decapping” activity consisting in removing the 5´cap of the mRNA rendering it accessible for being degradated by a 5´-3´ exonuclease [2].

The specificity of NUDT16 and its homologuous from Xenopus laevis X29 has been shown to be dependent of divalent cations required for hydrolysis. In vitro, when Mg2+ is added, the protein is only able to hydrolyze U8snoRNA whereas in presence of Mn2+ or Co2+ the activity is higher and the specificity is extended to other RNAs [3]. Structures of the both apo and holo- X29 protein of Xenopus laevis in complex with Mn2+ and m7GpppA were available[4].

We have solved the structure of human NUDT16 to a resolution of 1.8Å (PDB code : 3COU).. Applying a crystallographic symmetry operator on the monomer present in the asymmetrical unit allows retrieving the dimerical quaternary structure previously determined in the Xenopus homologous X29.

If the sequence identity between this X29 and NUDT16 is only 54%, residues involved in Mn2+ chelating and CAP binding are strictly conserved. One difference between these structures is that the side-chain of Glu158, involved in Mn2+ chelating, is in the same orientation as the corresponding residues (Glu150) in the holo-X29 despite the lack of a cation in this area.

References

  1. McLennan AG. The Nudix hydrolase superfamily Cell Mol Life Sci, 2006. 63(2): p. 123-43.
  2. Ghosh T, Peterson B, Tomasevic N and Peculis BA. Xenopus U8 snoRNA binding protein is a conserved nuclear decapping enzyme Mol Cell, 2004. 13(6): p. 817-28.
  3. Peculis BA, Reynolds K and Cleland M. Metal determines efficiency and substrate specificity of the nuclear NUDIX decapping proteins X29 and H29K (Nudt16) J Biol Chem, 2007. 282(34): p. 24792-805.
  4. Scarsdale JN, Peculis BA and Wright HT. Crystal structures of U8 snoRNA decapping nudix hydrolase, X29, and its metal and cap complexes Structure, 2006. 14(2): p. 331-43.