5obh: Difference between revisions
New page: '''Unreleased structure''' The entry 5obh is ON HOLD Authors: Dawson, A., Hunter, W.N., Jones, M. Description: Crystal structure of glycine binding protein in complex with bicuculline ... |
No edit summary |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of glycine binding protein in complex with bicuculline== | |||
<StructureSection load='5obh' size='340' side='right'caption='[[5obh]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5obh]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OBH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OBH FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=J94:(5S)-6,6-DIMETHYL-5-[(6R)-8-OXO-6,8-DIHYDROFURO[3,4-E][1,3]BENZODIOXOL-6-YL]-5,6,7,8-TETRAHYDRO[1,3]DIOXOLO[4,5-G]ISOQUINOLIN-6-IUM'>J94</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900017:triacetyl-beta-chitotriose'>PRD_900017</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5obh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5obh OCA], [https://pdbe.org/5obh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5obh RCSB], [https://www.ebi.ac.uk/pdbsum/5obh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5obh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bicuculline, a valued chemical tool in neurosciences research, is a competitive antagonist of specific GABAA receptors and affects other pentameric ligand-gated ion channels including the glycine, nicotinic acetylcholine and 5-hydroxytryptamine type 3 receptors. We used a fluorescence-quenching assay and isothermal titration calorimetry to record low-micromolar dissociation constants for N-methylbicuculline interacting with acetylcholine-binding protein and an engineered version called glycine-binding protein (GBP), which provides a surrogate for the heteromeric interface of the extracellular domain of the glycine receptor (GlyR). The 2.4 A resolution crystal structure of the GBP:N-methylbicuculline complex, sequence and structural alignments reveal similarities and differences between GlyR and the GABAA receptor-bicuculline interactions. N-methylbicuculline displays a similar conformation in different structures, but adopts distinct orientations enforced by interactions and steric blocks with key residues and plasticity in the binding sites. These features explain the promiscuous activity of bicuculline against the principal inhibitory pentameric ligand-gated ion channels in the CNS. | |||
A Structural Rationale for N-Methylbicuculline Acting as a Promiscuous Competitive Antagonist of Inhibitory Pentameric Ligand-Gated Ion Channels.,Jones MJ, Dawson A, Hales TG, Hunter WN Chembiochem. 2020 May 15;21(10):1526-1533. doi: 10.1002/cbic.201900680. Epub 2020, Feb 12. PMID:31859406<ref>PMID:31859406</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5obh" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aplysia californica]] | |||
[[Category: Large Structures]] | |||
[[Category: Dawson A]] | |||
[[Category: Hunter WN]] | |||
[[Category: Jones M]] | |||
Latest revision as of 12:39, 6 December 2023
Crystal structure of glycine binding protein in complex with bicucullineCrystal structure of glycine binding protein in complex with bicuculline
Structural highlights
FunctionPublication Abstract from PubMedBicuculline, a valued chemical tool in neurosciences research, is a competitive antagonist of specific GABAA receptors and affects other pentameric ligand-gated ion channels including the glycine, nicotinic acetylcholine and 5-hydroxytryptamine type 3 receptors. We used a fluorescence-quenching assay and isothermal titration calorimetry to record low-micromolar dissociation constants for N-methylbicuculline interacting with acetylcholine-binding protein and an engineered version called glycine-binding protein (GBP), which provides a surrogate for the heteromeric interface of the extracellular domain of the glycine receptor (GlyR). The 2.4 A resolution crystal structure of the GBP:N-methylbicuculline complex, sequence and structural alignments reveal similarities and differences between GlyR and the GABAA receptor-bicuculline interactions. N-methylbicuculline displays a similar conformation in different structures, but adopts distinct orientations enforced by interactions and steric blocks with key residues and plasticity in the binding sites. These features explain the promiscuous activity of bicuculline against the principal inhibitory pentameric ligand-gated ion channels in the CNS. A Structural Rationale for N-Methylbicuculline Acting as a Promiscuous Competitive Antagonist of Inhibitory Pentameric Ligand-Gated Ion Channels.,Jones MJ, Dawson A, Hales TG, Hunter WN Chembiochem. 2020 May 15;21(10):1526-1533. doi: 10.1002/cbic.201900680. Epub 2020, Feb 12. PMID:31859406[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||