4z90

ELIC bound with the anesthetic isoflurane in the resting state

spinqualitylabelsall models 4z90, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4z90 is a 10 chain structure with sequence from Dickeya dadantii 3937. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 4LE, MES Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E0SJQ4_DICD3 Publication Abstract from PubMed Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6') and A244(13'). A pore-radius contraction near the extracellular entrance was observed upon isoflurane binding. Electrophysiology measurements with a single-point mutation at position 6' or 13' support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs. Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.,Chen Q, Kinde MN, Arjunan P, Wells MM, Cohen AE, Xu Y, Tang P Sci Rep. 2015 Sep 8;5:13833. doi: 10.1038/srep13833. PMID:26346220 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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