Islam Md Mirazul, Aktaruzzaman M, Mohamed Zahurin
Pharmacogenomics Lab, Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Bioinformation. 2015 Feb 28;11(2):67-72. doi: 10.6026/97320630011067. eCollection 2015.
Normal blood glucose level depends on the availability of insulin and its ability to bind insulin receptor (IR) that regulates the downstream signaling pathway. Insulin sequence and blood glucose level usually vary among animals due to species specificity. The study of genetic variation of insulin, blood glucose level and diabetics symptoms development in Aves is interesting because of its optimal high blood glucose level than mammals. Therefore, it is of interest to study its evolutionary relationship with other mammals using sequence data. Hence, we compiled 32 Aves insulin from GenBank to compare its sequence-structure features with phylogeny for evolutionary inference. The analysis shows long conserved motifs (about 14 residues) for functional inference. These sequences show high leucine content (20%) with high instability index (>40). Amino acid position 11, 14, 16 and 20 are variable that may have contribution to binding to IR. We identified functionally critical variable residues in the dataset for possible genetic implication. Structural models of these sequences were developed for surface analysis towards functional representation. These data find application in the understanding of insulin function across species.
正常血糖水平取决于胰岛素的可用性及其与调节下游信号通路的胰岛素受体(IR)结合的能力。由于物种特异性,胰岛素序列和血糖水平在动物之间通常会有所不同。由于鸟类的血糖水平比哺乳动物高,因此研究鸟类胰岛素的遗传变异、血糖水平和糖尿病症状发展很有意思。因此,利用序列数据研究其与其他哺乳动物的进化关系很有意义。因此,我们从GenBank中收集了32种鸟类胰岛素,以比较其序列结构特征与系统发育,进行进化推断。分析显示出用于功能推断的长保守基序(约14个残基)。这些序列显示出高亮氨酸含量(20%)和高不稳定性指数(>40)。氨基酸位置11、14、16和20是可变的,可能有助于与IR结合。我们在数据集中确定了功能关键的可变残基,以探讨可能的遗传意义。开发了这些序列的结构模型,用于表面分析以进行功能表征。这些数据可用于理解跨物种的胰岛素功能。