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Comparative Computational Modeling of Agonist Binding to the Leukotriene Receptors BLT 1 and BLT 2
Molecular Biology ( IF 1.2 ) Pub Date : 2020-04-30 , DOI: 10.1134/s0026893320020107
G. F. Kurakin , N. P. Lopina , G. E. Bordina

Abstract—The

leukotriene B4 receptors BLT1 and BLT2 are promising targets for the treatment of allergic and inflammatory diseases. However, no working model of ligand binding to either of these receptors has been developed so far. Under the assumption that homologous receptors bind their ligands in a similar way, computational modeling of agonist binding to BLT1 and BLT2 was performed using fully flexible docking in Galaxy7TM. For both receptors, the carboxyl group of the ligand forms a salt bridge with an arginine residue, while the tail hydroxyl groups form hydrogen bonds with three amino acid residues. The differential specificity of ligands to BLT1 and BLT2 is explained by the replacement of histidine with tyrosine. In BLT1, the histidine residue binds the 5-OH group of the ligand, while the tyrosine residue in BLT2 repels it. The presented models are in agreement with experimental data and may be useful for developing new BLT1- and BLT2-targeted drugs.


中文翻译:

激动剂与白三烯受体BLT 1和BLT 2结合的比较计算模型

摘要

白三烯B 4受体BLT 1和BLT 2是治疗过敏性和炎性疾病的有希望的靶标。然而,到目前为止,尚未开发出与这些受体中的任一个结合的配体的工作模型。在同源受体以类似方式结合其配体的假设下,在Galaxy7TM中使用完全灵活的对接进行了激动剂与BLT 1和BLT 2结合的计算模型。对于两个受体,配体的羧基与精氨酸残基形成盐桥,而尾羟基与三个氨基酸残基形成氢键。配体对BLT 1和BLT 2的差异特异性用酪氨酸代替组氨酸来解释。在BLT 1中,组氨酸残基结合配体的5-OH基团,而在BLT 2中的酪氨酸残基将其排斥。提出的模型与实验数据相符,对于开发新的针对BLT 1和BLT 2的药物可能有用。
更新日期:2020-04-30
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