Format

Send to

Choose Destination
Acta Crystallogr D Biol Crystallogr. 2009 Apr;65(Pt 4):332-8. doi: 10.1107/S0907444909003102. Epub 2009 Mar 19.

Structure analysis of the conserved methyltransferase domain of human trimethylguanosine synthase TGS1.

Author information

1
Department of Molecular Structural Biology, Institute of Microbiology and Genetics, Georg-August-University Göttingen, Göttingen, Germany.

Abstract

Methyltransferases play an important role in the post-transcriptional maturation of most ribonucleic acids. The modification of spliceosomal UsnRNAs includes N2-dimethylation of the m(7)G cap catalyzed by trimethylguanosine synthase 1 (TGS1). This 5'-cap hypermethylation occurs during the biogenesis of UsnRNPs as it initiates the m(3)G cap-dependent nuclear import of UsnRNPs. The conserved methyltransferase domain of human TGS1 has been purified, crystallized and the crystal structure of this domain with bound substrate m(7)GpppA was solved by means of multiple-wavelength anomalous dispersion. Crystal structure analysis revealed that m(7)GpppA binds via its adenosine moiety to the structurally conserved adenosylmethionine-binding pocket, while the m(7) guanosine remains unbound. This unexpected binding only occurs in the absence of AdoMet and suggests an incomplete binding pocket for the m(7)G cap which is caused by the N-terminal truncation of the protein. These structural data are consistent with the finding that the crystallized fragment of human TGS1 is catalytically inactive, while a fragment that is 17 amino acids longer exhibits activity.

PMID:
19307714
DOI:
10.1107/S0907444909003102
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for International Union of Crystallography
Loading ...
Support Center