4qab: Difference between revisions
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The | ==X-RAY STRUCTURE of ACETYLCHOLINE BINDING PROTEIN (ACHBP) IN COMPLEX WITH 4-(MORPHOLIN-4-YL)-6-[4-(TRIFLUOROMETHYL)PHENYL]PYRIMIDIN-2-AMINE== | ||
<StructureSection load='4qab' size='340' side='right'caption='[[4qab]], [[Resolution|resolution]] 2.98Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4qab]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Lymnaea_stagnalis Lymnaea stagnalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QAB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QAB 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]] 2.984Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KK2:4-(MORPHOLIN-4-YL)-6-[4-(TRIFLUOROMETHYL)PHENYL]PYRIMIDIN-2-AMINE'>KK2</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'>[https://proteopedia.org/fgij/fg.htm?mol=4qab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qab OCA], [https://pdbe.org/4qab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qab RCSB], [https://www.ebi.ac.uk/pdbsum/4qab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qab ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ACHP_LYMST ACHP_LYMST] Binds to acetylcholine. Modulates neuronal synaptic transmission. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The nicotinic acetylcholine receptor (nAChR) and the acetylcholine binding protein (AChBP) are pentameric oligomers in which binding sites for nicotinic agonists and competitive antagonists are found at selected subunit interfaces. The nAChR spontaneously exists in multiple conformations associated with its activation and desensitization steps, and conformations are selectively stabilized by binding of agonists and antagonists. In the nAChR, agonist binding and the associated conformational changes accompanying activation and desensitization are cooperative. AChBP, which lacks the transmembrane spanning and cytoplasmic domains, serves as a homology model of the extracellular domain of the nAChRs. We identified unique cooperative binding behavior of a number of 4,6-disubstituted 2-aminopyrimidines to Lymnaea AChBP, with different molecular variants exhibiting positive, nH > 1.0, and negative cooperativity, nH < 1.0. Therefore, for a distinctive set of ligands, the extracellular domain of a nAChR surrogate suffices to accommodate cooperative interactions. X-ray crystal structures of AChBP complexes with examples of each allowed the identification of structural features in the ligands that confer differences in cooperative behavior. Both sets of molecules bind at the agonist-antagonist site, as expected from their competition with epibatidine. An analysis of AChBP quaternary structure shows that cooperative ligand binding is associated with a blooming or flare conformation, a structural change not observed with the classical, noncooperative, nicotinic ligands. Positively and negatively cooperative ligands exhibited unique features in the detailed binding determinants and poses of the complexes. | |||
Structural basis for cooperative interactions of substituted 2-aminopyrimidines with the acetylcholine binding protein.,Kaczanowska K, Harel M, Radic Z, Changeux JP, Finn MG, Taylor P Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10749-54. doi:, 10.1073/pnas.1410992111. Epub 2014 Jul 8. PMID:25006260<ref>PMID:25006260</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4qab" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Lymnaea stagnalis]] | |||
[[Category: Changeux J-P]] | |||
[[Category: Finn MG]] | |||
[[Category: Harel M]] | |||
[[Category: Kaczanowska K]] | |||
[[Category: Radic Z]] | |||
[[Category: Taylor P]] | |||
Latest revision as of 13:26, 30 October 2024
X-RAY STRUCTURE of ACETYLCHOLINE BINDING PROTEIN (ACHBP) IN COMPLEX WITH 4-(MORPHOLIN-4-YL)-6-[4-(TRIFLUOROMETHYL)PHENYL]PYRIMIDIN-2-AMINEX-RAY STRUCTURE of ACETYLCHOLINE BINDING PROTEIN (ACHBP) IN COMPLEX WITH 4-(MORPHOLIN-4-YL)-6-[4-(TRIFLUOROMETHYL)PHENYL]PYRIMIDIN-2-AMINE
Structural highlights
FunctionACHP_LYMST Binds to acetylcholine. Modulates neuronal synaptic transmission. Publication Abstract from PubMedThe nicotinic acetylcholine receptor (nAChR) and the acetylcholine binding protein (AChBP) are pentameric oligomers in which binding sites for nicotinic agonists and competitive antagonists are found at selected subunit interfaces. The nAChR spontaneously exists in multiple conformations associated with its activation and desensitization steps, and conformations are selectively stabilized by binding of agonists and antagonists. In the nAChR, agonist binding and the associated conformational changes accompanying activation and desensitization are cooperative. AChBP, which lacks the transmembrane spanning and cytoplasmic domains, serves as a homology model of the extracellular domain of the nAChRs. We identified unique cooperative binding behavior of a number of 4,6-disubstituted 2-aminopyrimidines to Lymnaea AChBP, with different molecular variants exhibiting positive, nH > 1.0, and negative cooperativity, nH < 1.0. Therefore, for a distinctive set of ligands, the extracellular domain of a nAChR surrogate suffices to accommodate cooperative interactions. X-ray crystal structures of AChBP complexes with examples of each allowed the identification of structural features in the ligands that confer differences in cooperative behavior. Both sets of molecules bind at the agonist-antagonist site, as expected from their competition with epibatidine. An analysis of AChBP quaternary structure shows that cooperative ligand binding is associated with a blooming or flare conformation, a structural change not observed with the classical, noncooperative, nicotinic ligands. Positively and negatively cooperative ligands exhibited unique features in the detailed binding determinants and poses of the complexes. Structural basis for cooperative interactions of substituted 2-aminopyrimidines with the acetylcholine binding protein.,Kaczanowska K, Harel M, Radic Z, Changeux JP, Finn MG, Taylor P Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10749-54. doi:, 10.1073/pnas.1410992111. Epub 2014 Jul 8. PMID:25006260[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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