5o87
Crystal structure of wild type Aplysia californica AChBP in complex with nicotineCrystal structure of wild type Aplysia californica AChBP in complex with nicotine
Structural highlights
FunctionPublication Abstract from PubMedProtein-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 alpha/beta glycine receptor. Engineering a surrogate human heteromeric alpha/beta glycine receptor orthosteric site exploiting the structural homology and stability of acetylcholine-binding protein.,Dawson A, Trumper P, de Souza JO, Parker H, Jones MJ, Hales TG, Hunter WN IUCrJ. 2019 Sep 4;6(Pt 6):1014-1023. doi: 10.1107/S205225251901114X. eCollection , 2019 Nov 1. PMID:31709057[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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