Kaczanowska, Katarzyna published the artcileStructural basis for cooperative interactions of substituted 2-aminopyrimidines with the acetylcholine binding protein, SDS of cas: 56-05-3, the publication is Proceedings of the National Academy of Sciences of the United States of America (2014), 111(29), 10749-10754, database is CAplus and MEDLINE.
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 homol. 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 mol. variants exhibiting pos., nH > 1.0, and neg. 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 mols. bind at the agonist-antagonist site, as expected from their competition with epibatidine. An anal. 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. Pos. and neg. cooperative ligands exhibited unique features in the detailed binding determinants and poses of the complexes.
Proceedings of the National Academy of Sciences of the United States of America published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, SDS of cas: 56-05-3.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia