5HCM
The GLIC pentameric Ligand-Gated Ion Channel 2-21' cross-linked mutant complexed to bromoform
Summary for 5HCM
| Entry DOI | 10.2210/pdb5hcm/pdb |
| Descriptor | Proton-gated ion channel, DODECYL-BETA-D-MALTOSIDE, TRIBROMOMETHANE (3 entities in total) |
| Functional Keywords | ion channel, receptor, anaesthetic, transport protein |
| Biological source | Gloeobacter violaceus |
| Cellular location | Cell inner membrane ; Multi- pass membrane protein : Q7NDN8 |
| Total number of polymer chains | 5 |
| Total formula weight | 181956.79 |
| Authors | Shahsavar, A.,Sauguet, L.,Delarue, M. (deposition date: 2016-01-04, release date: 2016-04-13, Last modification date: 2024-10-23) |
| Primary citation | Laurent, B.,Murail, S.,Shahsavar, A.,Sauguet, L.,Delarue, M.,Baaden, M. Sites of Anesthetic Inhibitory Action on a Cationic Ligand-Gated Ion Channel. Structure, 24:595-605, 2016 Cited by PubMed Abstract: Pentameric ligand-gated ion channels have been identified as the principal target of general anesthetics (GA), whose molecular mechanism of action remains poorly understood. Bacterial homologs, such as the Gloeobacter violaceus receptor (GLIC), have been shown to be valid functional models of GA action. The GA bromoform inhibits GLIC at submillimolar concentration. We characterize bromoform binding by crystallography and molecular dynamics (MD) simulations. GLIC's open form structure identified three intra-subunit binding sites. We crystallized the locally closed form with an additional bromoform molecule in the channel pore. We systematically compare binding with the multiple potential sites of allosteric channel regulation in the open, locally closed, and resting forms. MD simulations reveal differential exchange pathways between sites from one form to the other. GAs predominantly access the receptor from the lipid bilayer in all cases. Differential binding affinity among the channel forms is observed; the pore site markedly stabilizes the inactive versus active state. PubMed: 27021161DOI: 10.1016/j.str.2016.02.014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.15 Å) |
Structure validation
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