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Human NUDT6, N-terminal domain

PDB Code 3FXT Target Class Nucleotide metabolism Target NUDT6 Alias ASFGF2, bFGF, FGF-2, FGF-AS, FGF2AS, gfg, gfg-1, NUDT6 Disease Area/Function cancer Date Deposited Jan 21 2009 Authors Trésaugues, L., Welin, M., Arrowsmith, C.H., Berglund, H., Bountra, C., Collins, R., Dahlgren, L.G., Edwards, A.M., Flodin, S., Flores, A., Graslund, S., Hammarstrom, M., Johansson, A., Johansson, I., Karlberg, T., Kotenyova, T., Lehtio, L., Moche, M., Nilsson, M.E., Nyman, T., Persson, C., Sagemark, J., Schueler, H., Siponen, M.I., Thorsell, A.G., Van Den Berg, S., Weigelt, J., Welin, M., Wikstrom, M., Wisniewska, M., Nordlund, P. Related Structure 3H95

About this structure

The expression of fibroblast growth factor 2 (FGF-2) has been shown to be regulated by the mRNA whose DNA matrix is its antisense gene [1]. Both FGF-2 and FGF-2 antisense transcripts overlaps in their 3´ends, thus producing a stable double-stranded RNA duplex [2]. In addition, the FGF-2 antisense gene encodes a 316 amino-acid long protein which belongs to the family of the NUDIX hydrolases [3, 4], designed under the names of either NUDT6 or GFG. The functions and activity of this protein is only poorly described.

NUDT6 is constituted of two domains: a so far unknown domain lying between residues 45 and 134 and a NUDIX hydrolase domain encompassing residues 142 to 273.

SGC Stockholm has solved the crystallographic structure of the unknown N-terminal domain to a resolution of 2.3Ĺ. It was solved by MIRAS using Hg- and Sm-derivatized protein crystals. The structure solution was obtained thanks to the AutoSharp suite [5]. The asymmetrical unit shows eight chains organized in dimers whose interface burying about 1500Ĺ2. The N-terminal domain of NUDT6 is an α+β protein with a face composed of a 5 mixed strands β-sheet and one composed of 3 α-helices. The dimer organization produces an extended β-sheet. Structural comparisons reveal some similarities with multiple nucleic acids binding protein or domain.

References

  1. Li AW, Too CK, Knee R, Wilkinson M and Murphy PR. FGF-2 antisense RNA encodes a nuclear protein with MutT-like antimutator activity Mol Cell Endocrinol, 1997. 133(2): p. 177-82.
  2. Kimelman D and Kirschner MW. An antisense mRNA directs the covalent modification of the transcript encoding fibroblast growth factor in Xenopus oocytes Cell, 1989. 59(4): p. 687-96.
  3. Li AW, Too CK and Murphy PR. The basic fibroblast growth factor (FGF-2) antisense RNA (GFG) is translated into a MutT-related protein in vivo Biochem Biophys Res Commun, 1996. 223(1): p. 19-23.
  4. Koonin EV. A highly conserved sequence motif defining the family of MutT-related proteins from eubacteria, eukaryotes and viruses Nucleic Acids Res, 1993. 21(20): p. 4847.
  5. Vonrhein C, Blanc E, Roversi P and Bricogne G. Automated structure solution with autoSHARP Methods Mol Biol, 2007. 364: p. 215-30.