Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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 approximately 50A 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.

Original publication




Journal article


Febs lett

Publication Date





2959 - 2964


Amino Acid Substitution, Binding Sites, Crystallography, X-Ray, Dimerization, Distal Myopathies, Glycine-tRNA Ligase, Humans, Leucine, Models, Molecular, Muscular Atrophy, Spinal, Mutant Proteins, Mutation, Missense, RNA-Binding Proteins, Serine, Transfer RNA Aminoacylation