2q5h
Crystal structure of apo-wildtype Glycyl-tRNA synthetase
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OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Charcot-Marie-Tooth disease, type 2D OMIM:[600287], Neuropathy, distal hereditary motor, type V OMIM:[600287]
About this StructureAbout this Structure
2Q5H is a Single protein structure of sequence from Homo sapiens. Active as Glycine--tRNA ligase, with EC number 6.1.1.14 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy., Cader MZ, Ren J, James PA, Bird LE, Talbot K, Stammers DK, FEBS Lett. 2007 Jun 26;581(16):2959-2964. Epub 2007 May 29. PMID:17544401
Page seeded by OCA on Mon Nov 12 23:29:53 2007