5OAD
Crystal structure of mutant AChBP in complex with HEPES (T53F, Q74R, Y110A, I135S, G162E)
Summary for 5OAD
| Entry DOI | 10.2210/pdb5oad/pdb |
| Descriptor | Soluble acetylcholine receptor, 2-acetamido-2-deoxy-beta-D-glucopyranose, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (5 entities in total) |
| Functional Keywords | receptor, acetylcholine binding, signaling protein |
| Biological source | Aplysia californica (California sea hare) |
| Total number of polymer chains | 5 |
| Total formula weight | 143502.75 |
| Authors | Dawson, A.,Hunter, W.N.,de Souza, J.O.,Trumper, P. (deposition date: 2017-06-21, release date: 2018-08-01, Last modification date: 2024-01-17) |
| Primary citation | Dawson, A.,Trumper, P.,de Souza, J.O.,Parker, H.,Jones, M.J.,Hales, T.G.,Hunter, W.N. Engineering a surrogate human heteromeric alpha / beta glycine receptor orthosteric site exploiting the structural homology and stability of acetylcholine-binding protein. Iucrj, 6:1014-1023, 2019 Cited by PubMed Abstract: Protein-engineering methods have been exploited to produce a surrogate system for the extracellular neurotransmitter-binding site of a heteromeric human ligand-gated ion channel, the glycine receptor. This approach circumvents two major issues: the inherent experimental difficulties in working with a membrane-bound ion channel and the complication that a heteromeric assembly is necessary to create a key, physiologically relevant binding site. Residues that form the orthosteric site in a highly stable ortholog, acetylcholine-binding protein, were selected for substitution. Recombinant proteins were prepared and characterized in stepwise fashion exploiting a range of biophysical techniques, including X-ray crystallography, married to the use of selected chemical probes. The decision making and development of the surrogate, which is termed a glycine-binding protein, are described, and comparisons are provided with wild-type and homomeric systems that establish features of molecular recognition in the binding site and the confidence that the system is suited for use in early-stage drug discovery targeting a heteromeric α/β glycine receptor. PubMed: 31709057DOI: 10.1107/S205225251901114X PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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