6HJI
Xray structure of GLIC in complex with crotonate
Summary for 6HJI
| Entry DOI | 10.2210/pdb6hji/pdb |
| Descriptor | Proton-gated ion channel, DIUNDECYL PHOSPHATIDYL CHOLINE, CHLORIDE ION, ... (7 entities in total) |
| Functional Keywords | pentameric ligand-gated ion channel, membrane protein |
| Biological source | Gloeobacter violaceus |
| Total number of polymer chains | 5 |
| Total formula weight | 194788.64 |
| Authors | Fourati, Z.,Delarue, M. (deposition date: 2018-09-03, release date: 2019-09-18, Last modification date: 2024-05-15) |
| Primary citation | Fourati, Z.,Sauguet, L.,Delarue, M. Structural evidence for the binding of monocarboxylates and dicarboxylates at pharmacologically relevant extracellular sites of a pentameric ligand-gated ion channel. Acta Crystallogr D Struct Biol, 76:668-675, 2020 Cited by PubMed Abstract: GLIC is a bacterial homologue of the pentameric ligand-gated ion channels (pLGICs) that mediate the fast chemical neurotransmission of nerve signalling in eukaryotes. Because the activation and allosteric modulation features are conserved among prokaryotic and eukaryotic pLGICs, GLIC is commonly used as a model to study the allosteric transition and structural pharmacology of pLGICs. It has previously been shown that GLIC is inhibited by some carboxylic acid derivatives. Here, experimental evidence for carboxylate binding to GLIC is provided by solving its X-ray structures with a series of monocarboxylate and dicarboxylate derivatives, and two carboxylate-binding sites are described: (i) the `intersubunit' site that partially overlaps the canonical pLGIC orthosteric site and (ii) the `intrasubunit' vestibular site, which is only occupied by a subset of the described derivatives. While the intersubunit site is widely conserved in all pLGICs, the intrasubunit site is only conserved in cationic eukaryotic pLGICs. This study sheds light on the importance of these two extracellular modulation sites as potential drug targets in pLGICs. PubMed: 32627739DOI: 10.1107/S205979832000772X PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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