4qei

Two distinct conformational states of GlyRS captured in crystal lattice

spinqualitylabelsall models 4qei, resolution 2.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qei is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.875Å Ligands: AMP, GTP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GARS_HUMAN Autosomal dominant Charcot-Marie-Tooth disease type 2D;Distal hereditary motor neuropathy type 5. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Function GARS_HUMAN Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:28675565, PubMed:24898252). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis (PubMed:19710017). Publication Abstract from PubMed Glycyl-tRNA synthetase (GlyRS) is the enzyme that covalently links glycine to cognate tRNA for translation. It is of great research interest because of its nonconserved quaternary structures, unique species-specific aminoacylation properties, and noncanonical functions in neurological diseases, but none of these is fully understood. We report two crystal structures of human GlyRS variants, in the free form and in complex with tRNA(Gly) respectively, and reveal new aspects of the glycylation mechanism. We discover that insertion 3 differs considerably in conformation in catalysis and that it acts like a "switch" and fully opens to allow tRNA to bind in a cross-subunit fashion. The flexibility of the protein is supported by molecular dynamics simulation, as well as enzymatic activity assays. The biophysical and biochemical studies suggest that human GlyRS may utilize its flexibility for both the traditional function (regulate tRNA binding) and alternative functions (roles in diseases). Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis.,Deng X, Qin X, Chen L, Jia Q, Zhang Y, Zhang Z, Lei D, Ren G, Zhou Z, Wang Z, Li Q, Xie W J Biol Chem. 2016 Mar 11;291(11):5740-52. doi: 10.1074/jbc.M115.679126. Epub 2016, Jan 21. PMID:26797133 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminoacyl tRNA synthetase 3D structures

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