CAJ | 학술논문

用生物信息学的方法分析不同物种的α-葡糖糖苷酶的亲缘关系,分析降血糖药物米格列醇与甜菜( Beta vulgaris)的α-葡糖糖苷酶相互作用位点在其他亲缘关系较近的物种中相应的氨基酸变化特点,结果表明米格列醇位于一个凹向酶分子内部的狭窄的结合口袋中,其间的相互作用主要以静电相互作用、氢键和范德华力为主. 由于米格列醇的强水溶性和多羟基的特点,与酸性的天冬氨酸之间形成多个O-H氢键,对甜菜( Beta vulgaris)的α-葡萄糖苷酶具有较好的抑制作用. 通过TM-HMM预测甜菜( Beta vulgaris)的α-葡萄糖苷酶的序列,结果未发现跨膜区. 通过多序列比对发现,在米格列醇与甜菜( Beta vulgaris)的α-葡萄糖苷酶相互作用位点处的氨基酸中,在与其亲缘关系较近的5个物种茶( Camellia sinensis) ,黄瓜( Cucumis sativus),木本棉(Gossypium arboretum),甘庶属割手密(Spontaneum)和蒺藜状苜蓿(Medicago truncatula)中有81.82%的氨基酸都是保守的,且主要是极性的氨基酸,如色氨酸和天冬氨酸. 这为进一步研究降血糖药物在其他物种中的表现及相互作用提供了重要的科学依据.
용생물신식학적방법분석불동물충적α-포당당감매적친연관계,분석강혈당약물미격렬순여첨채( Beta vulgaris)적α-포당당감매상호작용위점재기타친연관계교근적물충중상응적안기산변화특점,결과표명미격렬순위우일개요향매분자내부적협착적결합구대중,기간적상호작용주요이정전상호작용、경건화범덕화력위주. 유우미격렬순적강수용성화다간기적특점,여산성적천동안산지간형성다개O-H경건,대첨채( Beta vulgaris)적α-포도당감매구유교호적억제작용. 통과TM-HMM예측첨채( Beta vulgaris)적α-포도당감매적서렬,결과미발현과막구. 통과다서렬비대발현,재미격렬순여첨채( Beta vulgaris)적α-포도당감매상호작용위점처적안기산중,재여기친연관계교근적5개물충다( Camellia sinensis) ,황과( Cucumis sativus),목본면(Gossypium arboretum),감서속할수밀(Spontaneum)화질려상목숙(Medicago truncatula)중유81.82%적안기산도시보수적,차주요시겁성적안기산,여색안산화천동안산. 저위진일보연구강혈당약물재기타물충중적표현급상호작용제공료중요적과학의거.
The phylogenetic relationship of α-glucosidase between different species was analyzed by using the method of bioinformatics. By analyzing the interaction site between the hypoglycemic drug Miglitol andα-glucosidase of Beta vulgaris, and the characteristics of corresponding amino acid in other close genetic species, we found that Miglitol was located in a narrow binding pocket which recesses inside to the enzyme molecule. The interactions between them are mainly electrostatic interactions, hydrogen bonds and van der Waals forces. There are multiple O-H hydrogen bonds between drug and the enzyme molecules, which makes Miglitol a better inhibition because of the characteristics of strong water-solubility and polyhydroxy of the Miglitol. Through TMHMM prediction of the Beta vulgaris α-glucosidase sequence, it was found that there is no transmembrane region. The multiple sequence alignment suggested that 81.82% of the amino acids located in the interactive sites between Miglitol and Beta vulgarisα-glucosidase were conservative among the closest genetic species Camellia sinensis, Cucumis sativus, Gossypium arboretum, Spontaneum and Medicago truncatula. Among the conserved amino acids, the polar ones, such as Asp and Trp, were the most. This bioinformatics-based analysis can provide important scientific basis for further behavioral research of the hypoglycemic drugs in other species.