一个OGT基因与糖尿病相关性的in-silico分析
Abigail O Ayodele1, Brenda Udosen1,2, Olugbenga O Oluwagbemi3,4
1H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria.
与O相关的N-乙糖胺转移酶 (OGT) 的遗传变异可能会影响糖尿病. 这项研究确定了7个显著的OGTSNP,并模拟了它们与OGT抑制剂的相互作用,表明了潜在的药物标.
科学领域:
- 生物化学 生物化学
- 遗传学 遗传学 是一个
- 结构生物学 结构生物学
背景情况:
- O-GlcNAcylation是一种关键的营养感应后翻译修饰,涉及O-链接的N-乙糖胺转移酶 (OGT) 和O-GlcNAcase (OGA).
- 异常的OGT表达与代谢疾病有关,包括癌症和糖尿病 (DM).
- 了解OGT遗传变异的功能影响对于疾病研究至关重要.
研究的目的:
- 在OGT基因中识别和分析临床上显著的单核酸多态 (SNP).
- 预测这些OGT SNP的功能影响和结构影响.
- 评估已知的OGT抑制剂对突变的OGT蛋白质模型的结合亲和力.
主要方法:
- 从数据库中检索出 159 个临床意义上的 OGT SNP.
- 使用生物信息学工具 (PhD-SNPs,SNPs&Go,PROVEAN,PolyPhen2) 来预测SNP的有害性.
- 采用同质模型 (ROBETTA) 和分子对接 (Schrodinger Maestro) 来评估蛋白质结构和连接体相互作用.
主要成果:
- 鉴定了7种有害的OGTSNP (G103R,N196K,Y228H,R250C,G341V,L367F,C845S).这些SNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTSNP中,OGTS中,OGTS中,OGTS中,OGTS中,OGTS中,OGTN中,OGTN中,OGTN中,OGTN中,OGTN中,OGTN中,OGTN中.
- 建模了突变的OGT蛋白质,并与OGT抑制剂OSMI-1进行对接.
- 观察到OSMI-1和突变的OGT模型的活性部位之间存在强烈的结合亲缘关系.
结论:
- 鉴定到的OGT突变点显示出重要的预测有害影响.
- 这些突变的OGT变体与OGT抑制剂OSMI-1具有良好的相互作用.
- 这些发现表明,针对OGT治疗糖尿病的潜在治疗策略.
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