5cmc

Mnemiopsis leidyi ML032222a iGluR LBD E423S mutant glycine complex

spinqualitylabelsall models 5cmc, resolution 1.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cmc is a 2 chain structure with sequence from Mnemiopsis leidyi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.28Å Ligands: GLY, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0R4I973_MNELE Publication Abstract from PubMed The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine. X-ray crystallographic analysis details rearrangements in the binding pocket stemming from the mutations, and molecular dynamics simulations suggest that the interdomain salt bridge acts as a steric barrier regulating ligand binding and that the free energy required to access open conformations in the glycine-bound LBD is largely responsible for differences in ligand affinity among the LBD variants. Molecular lock regulates binding of glycine to a primitive NMDA receptor.,Yu A, Alberstein R, Thomas A, Zimmet A, Grey R, Mayer ML, Lau AY Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):E6786-E6795. Epub 2016 Oct 17. PMID:27791085 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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