6t9r: Difference between revisions
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<StructureSection load='6t9r' size='340' side='right'caption='[[6t9r]], [[Resolution|resolution]] 1.72Å' scene=''> | <StructureSection load='6t9r' size='340' side='right'caption='[[6t9r]], [[Resolution|resolution]] 1.72Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6t9r]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T9R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6T9R FirstGlance]. <br> | <table><tr><td colspan='2'>[[6t9r]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Aplca Aplca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T9R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6T9R FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MXQ:(1~{R},9~{S})-5-(3-oxidanylpropyl)-7,11-diazatricyclo[7.3.1.0^{2,7}]trideca-2,4-dien-6-one'>MXQ</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"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MXQ:(1~{R},9~{S})-5-(3-oxidanylpropyl)-7,11-diazatricyclo[7.3.1.0^{2,7}]trideca-2,4-dien-6-one'>MXQ</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6t9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t9r OCA], [http://pdbe.org/6t9r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t9r RCSB], [http://www.ebi.ac.uk/pdbsum/6t9r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t9r ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6t9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t9r OCA], [http://pdbe.org/6t9r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t9r RCSB], [http://www.ebi.ac.uk/pdbsum/6t9r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t9r ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cytisine, a natural product with high affinity for clinically relevant nicotinic acetylcholine receptors (nAChRs), is used as a smoking-cessation agent. The compound displays an excellent clinical profile and hence there is an interest in derivatives that may be further improved or find use in the treatment of other conditions. Here, the binding of a cytisine derivative modified by the addition of a 3-(hydroxypropyl) moiety (ligand 4) to Aplysia californica acetylcholine-binding protein (AcAChBP), a surrogate for nAChR orthosteric binding sites, was investigated. Isothermal titration calorimetry revealed that the favorable binding of cytisine and its derivative to AcAChBP is driven by the enthalpic contribution, which dominates an unfavorable entropic component. Although ligand 4 had a less unfavorable entropic contribution compared with cytisine, the affinity for AcAChBP was significantly diminished owing to the magnitude of the reduction in the enthalpic component. The high-resolution crystal structure of the AcAChBP-4 complex indicated close similarities in the protein-ligand interactions involving the parts of 4 common to cytisine. The point of difference, the 3-(hydroxypropyl) substituent, appears to influence the conformation of the Met133 side chain and helps to form an ordered solvent structure at the edge of the orthosteric binding site. | |||
The thermodynamic profile and molecular interactions of a C(9)-cytisine derivative-binding acetylcholine-binding protein from Aplysia californica.,Davis S, Rego Campello H, Gallagher T, Hunter WN Acta Crystallogr F Struct Biol Commun. 2020 Feb 1;76(Pt 2):74-80. doi:, 10.1107/S2053230X20001168. Epub 2020 Feb 3. PMID:32039888<ref>PMID:32039888</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6t9r" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Aplca]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Davis, S]] | [[Category: Davis, S]] | ||
Revision as of 10:37, 19 February 2020
Aplysia californica AChBP in complex with a cytisine derivativeAplysia californica AChBP in complex with a cytisine derivative
Structural highlights
Publication Abstract from PubMedCytisine, a natural product with high affinity for clinically relevant nicotinic acetylcholine receptors (nAChRs), is used as a smoking-cessation agent. The compound displays an excellent clinical profile and hence there is an interest in derivatives that may be further improved or find use in the treatment of other conditions. Here, the binding of a cytisine derivative modified by the addition of a 3-(hydroxypropyl) moiety (ligand 4) to Aplysia californica acetylcholine-binding protein (AcAChBP), a surrogate for nAChR orthosteric binding sites, was investigated. Isothermal titration calorimetry revealed that the favorable binding of cytisine and its derivative to AcAChBP is driven by the enthalpic contribution, which dominates an unfavorable entropic component. Although ligand 4 had a less unfavorable entropic contribution compared with cytisine, the affinity for AcAChBP was significantly diminished owing to the magnitude of the reduction in the enthalpic component. The high-resolution crystal structure of the AcAChBP-4 complex indicated close similarities in the protein-ligand interactions involving the parts of 4 common to cytisine. The point of difference, the 3-(hydroxypropyl) substituent, appears to influence the conformation of the Met133 side chain and helps to form an ordered solvent structure at the edge of the orthosteric binding site. The thermodynamic profile and molecular interactions of a C(9)-cytisine derivative-binding acetylcholine-binding protein from Aplysia californica.,Davis S, Rego Campello H, Gallagher T, Hunter WN Acta Crystallogr F Struct Biol Commun. 2020 Feb 1;76(Pt 2):74-80. doi:, 10.1107/S2053230X20001168. Epub 2020 Feb 3. PMID:32039888[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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