Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2050981 | FEBS Letters | 2007 | 6 Pages |
Abstract
Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), including S581L, lead to motor nerve degeneration. We have determined crystal structures of wildtype and S581L-mutant human GlyRS. The S581L mutation is ∼50 Å from the active site, and yet gives reduced aminoacylation activity. The overall structures of wildtype and S581L-GlyRS, including the active site, are very similar. However, residues 567–575 of the anticodon-binding domain shift position and in turn could indirectly affect glycine binding via the tRNA or alternatively inhibit conformational changes. Reduced enzyme activity may underlie neuronal degeneration, although a dominant-negative effect is more likely in this autosomal dominant disorder.
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Authors
Muhammed Z. Cader, Jingshan Ren, Paul A. James, Louise E. Bird, Kevin Talbot, David K. Stammers,