{"title":"结构洞察和计算分子对接探索STAT3新的治疗药物靶点","authors":"","doi":"10.47262/bl/9.1.20230421","DOIUrl":null,"url":null,"abstract":"Signal transducer and activator of transcription 3 (STAT3) is a transcription factor, that contains a DNA-binding domain, N-terminal domain, and SH2 domain. The dysregulation of STAT3 activity has been associated with various diseases, such as chronic inflammation and autoimmune disorders. In cancer, STAT3 is often constitutively activated and promotes tumor cell survival, proliferation, and immune evasion. Various bioinformatics approaches were employed to predict the 3D structure of STAT3, followed by a comprehensive evaluation of the predicted model. 3D predicted structure of the target protein revealed an overall quality factor of 94. 45%. It was also observed through the Ramachandran plot that 1.26% residues of the predicted structure of STAT3 were present in the outlier region of the protein structure. Computational docking studies were done to identify the novel drug targets against STAT3. The screened compound via high throughput virtual screening may have the potential to regulate the activity of STAT3. The lowest binding energy of -8.7 Kcal/mol was observed. His-457, Tyr-456, Lys-488, Pro-487, Gln-326, Leu-459, Lys-244, Gln-247 conserved residues were observed. The structural insight and functional determination of STAT3 depend on the identification of the potent binding domain in protein 3D structure.","PeriodicalId":9154,"journal":{"name":"Biomedical Letters","volume":"90 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Structural insights and computational molecular docking to explore novel therapeutic drug targets of STAT3\",\"authors\":\"\",\"doi\":\"10.47262/bl/9.1.20230421\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Signal transducer and activator of transcription 3 (STAT3) is a transcription factor, that contains a DNA-binding domain, N-terminal domain, and SH2 domain. The dysregulation of STAT3 activity has been associated with various diseases, such as chronic inflammation and autoimmune disorders. In cancer, STAT3 is often constitutively activated and promotes tumor cell survival, proliferation, and immune evasion. Various bioinformatics approaches were employed to predict the 3D structure of STAT3, followed by a comprehensive evaluation of the predicted model. 3D predicted structure of the target protein revealed an overall quality factor of 94. 45%. It was also observed through the Ramachandran plot that 1.26% residues of the predicted structure of STAT3 were present in the outlier region of the protein structure. Computational docking studies were done to identify the novel drug targets against STAT3. The screened compound via high throughput virtual screening may have the potential to regulate the activity of STAT3. The lowest binding energy of -8.7 Kcal/mol was observed. His-457, Tyr-456, Lys-488, Pro-487, Gln-326, Leu-459, Lys-244, Gln-247 conserved residues were observed. The structural insight and functional determination of STAT3 depend on the identification of the potent binding domain in protein 3D structure.\",\"PeriodicalId\":9154,\"journal\":{\"name\":\"Biomedical Letters\",\"volume\":\"90 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-06-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical Letters\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.47262/bl/9.1.20230421\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Letters","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.47262/bl/9.1.20230421","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
STAT3 (Signal transducer and activator of transcription 3)是一种转录因子,包含dna结合域、n端结构域和SH2结构域。STAT3活性的失调与多种疾病有关,如慢性炎症和自身免疫性疾病。在癌症中,STAT3经常被组成性激活,促进肿瘤细胞存活、增殖和免疫逃避。采用多种生物信息学方法预测STAT3的三维结构,然后对预测模型进行综合评估。三维预测的目标蛋白结构显示,总体质量因子为94。45%。通过Ramachandran图也观察到1.26%的预测结构残基存在于STAT3蛋白结构的离群区。通过计算对接研究来确定针对STAT3的新型药物靶点。通过高通量虚拟筛选筛选的化合物可能具有调节STAT3活性的潜力。最低结合能为-8.7 Kcal/mol。观察到His-457、Tyr-456、Lys-488、Pro-487、Gln-326、Leu-459、Lys-244、Gln-247等保守残基。STAT3的结构洞察和功能确定依赖于蛋白质三维结构中有效结合域的识别。
Structural insights and computational molecular docking to explore novel therapeutic drug targets of STAT3
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor, that contains a DNA-binding domain, N-terminal domain, and SH2 domain. The dysregulation of STAT3 activity has been associated with various diseases, such as chronic inflammation and autoimmune disorders. In cancer, STAT3 is often constitutively activated and promotes tumor cell survival, proliferation, and immune evasion. Various bioinformatics approaches were employed to predict the 3D structure of STAT3, followed by a comprehensive evaluation of the predicted model. 3D predicted structure of the target protein revealed an overall quality factor of 94. 45%. It was also observed through the Ramachandran plot that 1.26% residues of the predicted structure of STAT3 were present in the outlier region of the protein structure. Computational docking studies were done to identify the novel drug targets against STAT3. The screened compound via high throughput virtual screening may have the potential to regulate the activity of STAT3. The lowest binding energy of -8.7 Kcal/mol was observed. His-457, Tyr-456, Lys-488, Pro-487, Gln-326, Leu-459, Lys-244, Gln-247 conserved residues were observed. The structural insight and functional determination of STAT3 depend on the identification of the potent binding domain in protein 3D structure.