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==Crystal Structure of Human Glycine Receptor alpha-3 Bound to AM-3607, Glycine, and Ivermectin== | ==Crystal Structure of Human Glycine Receptor alpha-3 Bound to AM-3607, Glycine, and Ivermectin== | ||
<StructureSection load='5vdh' size='340' side='right' caption='[[5vdh]], [[Resolution|resolution]] 2.85Å' scene=''> | <StructureSection load='5vdh' size='340' side='right'caption='[[5vdh]], [[Resolution|resolution]] 2.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5vdh]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VDH OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5vdh]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VDH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VDH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7C6:(3S,3AS,9BS)-2-[(2H-1,3-BENZODIOXOL-5-YL)SULFONYL]-3,5-DIMETHYL-1,2,3,3A,5,9B-HEXAHYDRO-4H-PYRROLO[3,4-C][1,6]NAPHTHYRIDIN-4-ONE'>7C6</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=IVM:(2AE,4E,5S,6S,6R,7S,8E,11R,13R,15S,17AR,20R,20AR,20BS)-6-[(2S)-BUTAN-2-YL]-20,20B-DIHYDROXY-5,6,8,19-TETRAMETHYL-17-OXO-3,4,5,6,6,10,11,14,15,17,17A,20,20A,20B-TETRADECAHYDRO-2H,7H-SPIRO[11,15-METHANOFURO[4,3,2-PQ][2,6]BENZODIOXACYCLOOCTADECINE-13,2-PYRAN]-7-YL+2,6-DIDEOXY-4-O-(2,6-DIDEOXY-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSYL)-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSIDE'>IVM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7C6:(3S,3AS,9BS)-2-[(2H-1,3-BENZODIOXOL-5-YL)SULFONYL]-3,5-DIMETHYL-1,2,3,3A,5,9B-HEXAHYDRO-4H-PYRROLO[3,4-C][1,6]NAPHTHYRIDIN-4-ONE'>7C6</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=IVM:(2AE,4E,5S,6S,6R,7S,8E,11R,13R,15S,17AR,20R,20AR,20BS)-6-[(2S)-BUTAN-2-YL]-20,20B-DIHYDROXY-5,6,8,19-TETRAMETHYL-17-OXO-3,4,5,6,6,10,11,14,15,17,17A,20,20A,20B-TETRADECAHYDRO-2H,7H-SPIRO[11,15-METHANOFURO[4,3,2-PQ][2,6]BENZODIOXACYCLOOCTADECINE-13,2-PYRAN]-7-YL+2,6-DIDEOXY-4-O-(2,6-DIDEOXY-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSYL)-3-O-METHYL-ALPHA-L-ARABINO-HEXOPYRANOSIDE'>IVM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5vdh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vdh OCA], [https://pdbe.org/5vdh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vdh RCSB], [https://www.ebi.ac.uk/pdbsum/5vdh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vdh ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/GLRA3_HUMAN GLRA3_HUMAN] The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing). | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 23: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Chen H]] | ||
[[Category: | [[Category: Huang X]] | ||
[[Category: | [[Category: Shaffer PL]] | ||
Latest revision as of 16:46, 4 October 2023
Crystal Structure of Human Glycine Receptor alpha-3 Bound to AM-3607, Glycine, and IvermectinCrystal Structure of Human Glycine Receptor alpha-3 Bound to AM-3607, Glycine, and Ivermectin
Structural highlights
FunctionGLRA3_HUMAN The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing). Publication Abstract from PubMedIvermectin acts as a positive allosteric modulator of several Cys-loop receptors including the glutamate-gated chloride channels (GluCls), gamma-aminobutyric acid receptors (GABAARs), glycine receptors (GlyRs), and neuronal alpha7-nicotinic receptors (alpha7 nAChRs). The crystal structure of Caenorhabditis elegans GluCl complexed with ivermectin revealed the details of its ivermectin binding site. Although the electron microscopy structure of zebrafish GlyRalpha1 complexed with ivermectin demonstrated a similar binding orientation, detailed structural information on the ivermectin binding and pore opening for Cys-loop receptors in vertebrates has been elusive. Here we present the crystal structures of human GlyRalpha3 in complex with ivermectin at 2.85 and 3.08 A resolution. Our structures allow us to explore in detail the molecular recognition of ivermectin by GlyRs, GABAARs, and alpha7 nAChRs. Comparisons with previous structures reveal how the ivermectin binding expands the ion channel pore. Our results hold promise in structure-based design of GlyR modulators for the treatment of neuropathic pain. Crystal Structures of Human GlyRalpha3 Bound to Ivermectin.,Huang X, Chen H, Shaffer PL Structure. 2017 May 4. pii: S0969-2126(17)30108-9. doi:, 10.1016/j.str.2017.04.007. PMID:28479061[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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