5oaj: Difference between revisions
New page: '''Unreleased structure''' The entry 5oaj is ON HOLD until Paper Publication Authors: Dawson, A., Hunter, W.N., de Souza, J.O., Trumper, P. Description: Crystal structure of mutant ACh... |
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==Crystal structure of mutant AChBP in complex with tropisetron (T53F, Q74R, Y110A, I135S, G162E)== | |||
<StructureSection load='5oaj' size='340' side='right'caption='[[5oaj]], [[Resolution|resolution]] 2.47Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5oaj]] is a 10 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=5OAJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OAJ 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]] 2.47Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TKT:(3-ENDO)-8-METHYL-8-AZABICYCLO[3.2.1]OCT-3-YL+1H-INDOLE-3-CARBOXYLATE'>TKT</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=5oaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oaj OCA], [https://pdbe.org/5oaj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oaj RCSB], [https://www.ebi.ac.uk/pdbsum/5oaj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oaj ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein-engineering methods have been exploited to produce a surrogate system for the extracellular neurotransmitter-binding site of a heteromeric human ligand-gated ion channel, the glycine receptor. This approach circumvents two major issues: the inherent experimental difficulties in working with a membrane-bound ion channel and the complication that a heteromeric assembly is necessary to create a key, physiologically relevant binding site. Residues that form the orthosteric site in a highly stable ortholog, acetylcholine-binding protein, were selected for substitution. Recombinant proteins were prepared and characterized in stepwise fashion exploiting a range of biophysical techniques, including X-ray crystallography, married to the use of selected chemical probes. The decision making and development of the surrogate, which is termed a glycine-binding protein, are described, and comparisons are provided with wild-type and homomeric systems that establish features of molecular recognition in the binding site and the confidence that the system is suited for use in early-stage drug discovery targeting a heteromeric alpha/beta glycine receptor. | |||
Engineering a surrogate human heteromeric alpha/beta glycine receptor orthosteric site exploiting the structural homology and stability of acetylcholine-binding protein.,Dawson A, Trumper P, de Souza JO, Parker H, Jones MJ, Hales TG, Hunter WN IUCrJ. 2019 Sep 4;6(Pt 6):1014-1023. doi: 10.1107/S205225251901114X. eCollection , 2019 Nov 1. PMID:31709057<ref>PMID:31709057</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5oaj" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: Trumper | *[[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: Trumper P]] | |||
[[Category: De Souza JO]] | |||
Latest revision as of 12:38, 6 December 2023
Crystal structure of mutant AChBP in complex with tropisetron (T53F, Q74R, Y110A, I135S, G162E)Crystal structure of mutant AChBP in complex with tropisetron (T53F, Q74R, Y110A, I135S, G162E)
Structural highlights
FunctionPublication Abstract from PubMedProtein-engineering methods have been exploited to produce a surrogate system for the extracellular neurotransmitter-binding site of a heteromeric human ligand-gated ion channel, the glycine receptor. This approach circumvents two major issues: the inherent experimental difficulties in working with a membrane-bound ion channel and the complication that a heteromeric assembly is necessary to create a key, physiologically relevant binding site. Residues that form the orthosteric site in a highly stable ortholog, acetylcholine-binding protein, were selected for substitution. Recombinant proteins were prepared and characterized in stepwise fashion exploiting a range of biophysical techniques, including X-ray crystallography, married to the use of selected chemical probes. The decision making and development of the surrogate, which is termed a glycine-binding protein, are described, and comparisons are provided with wild-type and homomeric systems that establish features of molecular recognition in the binding site and the confidence that the system is suited for use in early-stage drug discovery targeting a heteromeric alpha/beta glycine receptor. Engineering a surrogate human heteromeric alpha/beta glycine receptor orthosteric site exploiting the structural homology and stability of acetylcholine-binding protein.,Dawson A, Trumper P, de Souza JO, Parker H, Jones MJ, Hales TG, Hunter WN IUCrJ. 2019 Sep 4;6(Pt 6):1014-1023. doi: 10.1107/S205225251901114X. eCollection , 2019 Nov 1. PMID:31709057[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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