2yme: Difference between revisions
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<StructureSection load='2yme' size='340' side='right'caption='[[2yme]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='2yme' size='340' side='right'caption='[[2yme]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2yme]] is a 10 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2yme]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Aplca Aplca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YME OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YME FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CWB:1-METHYL-N-[(1R,5S)-9-METHYL-9-AZABICYCLO[3.3.1]NONAN-3-YL]INDAZOLE-3-CARBOXAMIDE'>CWB</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CWB:1-METHYL-N-[(1R,5S)-9-METHYL-9-AZABICYCLO[3.3.1]NONAN-3-YL]INDAZOLE-3-CARBOXAMIDE'>CWB</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ymd|2ymd]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ymd|2ymd]]</div></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=2yme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yme OCA], [https://pdbe.org/2yme PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yme RCSB], [https://www.ebi.ac.uk/pdbsum/2yme PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yme ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
Revision as of 15:32, 27 April 2022
Crystal structure of a mutant binding protein (5HTBP-AChBP) in complex with granisetronCrystal structure of a mutant binding protein (5HTBP-AChBP) in complex with granisetron
Structural highlights
Publication Abstract from PubMedThe 5-HT3 receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT3 receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation-pi interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT3 receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT3 receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT3 receptor. Structural basis of ligand recognition in 5-HT3 receptors.,Kesters D, Thompson AJ, Brams M, van Elk R, Spurny R, Geitmann M, Villalgordo JM, Guskov A, Helena Danielson U, Lummis SC, Smit AB, Ulens C EMBO Rep. 2012 Nov 30. doi: 10.1038/embor.2012.189. PMID:23196367[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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