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脂肪酸结合蛋白4(Fatty Acid Binding Protein 4,FABP4)作为脂肪酸伴侣,参与调节脂肪酸代谢、运输、脂介导的信号转导以及巨噬细胞的炎症反应。该蛋白的抑制经常作为治疗脂肪代谢疾病的有效方案。本文报道了经典非甾体抗炎药阿司匹林及其水解物水杨酸与FABP4蛋白复合物的晶体结构,从而推测阿司匹林可能通过FABP4蛋白途径抑制动脉粥样硬化的分子机制。结构分析进一步阐明了FABP4蛋白疏水残基Phe16苯环侧链与水杨酸之间的C-H-π相互作用比亲水位点静电相互作用提供更稳定的结合。该发现为设计更高选择性FABP4抑制剂提供了新的途径。
Fatty Acid Binding Protein 4 (FABP4), a fatty acid chaperone, is involved in the regulation of fatty acid metabolism, trafficking, lipid-mediated signal transduction, and macrophage inflammatory responses. Inhibition of this protein is often used as an effective treatment for diseases of fat metabolism. In this paper, we report the crystal structure of aspirin, a classic nonsteroidal anti-inflammatory drug, and its hydrolyzate, salicylic acid, and FABP4 protein complexes. Thus, we speculate that aspirin may inhibit the molecular mechanism of atherosclerosis via the FABP4 protein pathway. Structural analysis further elucidates that the C-H-π interaction between the Phe16 benzene ring side chain of the FABP4 protein hydrophobic residue and salicylic acid provides more stable binding than the electrostatic interaction of the hydrophilic sites. This finding provides a new avenue for designing more selective FABP4 inhibitors.