PDBsum entry 2q5h

Ligase

PDB id: 2q5h

Contents

Protein chain

528 a.a.

Waters ×10

References listed in PDB file

Key reference

• Title: Crystal structure of human wildtype and s581l-Mutant glycyl-Trna synthetase, An enzyme underlying distal spinal muscular atrophy.
• Authors: M.Z.Cader, J.Ren, P.A.James, L.E.Bird, K.Talbot, D.K.Stammers.
• Ref.: Febs Lett, 2007, 581, 2959-2964.
• PubMed id: 17544401

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 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.