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A novel capillary‐based microfluidic strategy to accelerate the process of small‐molecule‐compound screening by room‐temperature X‐ray crystallography using protein crystals is reported. The ultra‐thin microfluidic devices are composed of a UV‐curable polymer, patterned by cleanroom photolithography, and have nine capillary channels per chip. The chip was designed for ease of sample manipulation,...
The structural basis for alcohol modulation of neuronal pentameric ligand-gated ion channels (pLGICs) remains elusive. We determined an inhibitory mechanism of alcohol on the pLGIC Erwinia chrysanthemi (ELIC) through direct binding to the pore. X-ray structures of ELIC co-crystallized with 2-bromoethanol, in both the absence and presence of agonist, reveal 2-bromoethanol binding in the pore near T237(6′)...
Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but a structural understanding of anesthetic action on pLGICs remains elusive. GLIC, a prokaryotic pLGIC, can be inhibited by anesthetics, including ketamine. The ketamine concentration leading to half-maximal inhibition of GLIC (58 μM) is comparable to that on neuronal nicotinic acetylcholine receptors. A 2.99 Å resolution...
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