摘要
目的利用血清学及PacBio三代测序技术鉴定1例罕见cisAB亚型,利用分子对接探讨糖基转移酶氨基酸突变导致亚型的分子机制。方法利用免疫血清学试验鉴定ABO表型,利用PacBio三代测序方法鉴定其基因型。突变后的糖基转移酶同源建模和分子对接后,与野生型α1,3-N-乙酰氨基半乳糖转移酶(α1-3-N-acetylgalactosaminyltransferase,GTA)进行结构叠加和比对,探究关键位点氨基酸突变后糖基转移酶的结构变化。结果免疫血清学试验鉴定表型为AB型,三代基因测序技术结果显示该患者基因型为cisAB.01/O.01.02,分子对接结果显示与野生型相比,cisAB01糖基转移酶p.Pro156Leu和p.Gly268Ala突变导致临近氨基酸结构朝向改变,催化口袋凹槽结构改变,出现双功能酶活性。结论p.Pro156Leu和p.Gly268Ala突变是形成cisAB01糖基转移酶双功能活性的关键位点。
Objective To identify a rare cisAB subtype by immunoserology and PacBio third-generation sequencing technology,and explore the molecular mechanism of amino acid mutations in cisAB glycosyltransferase by molecular docking.Methods The ABO phenotype was identified by immunoserological method,and the genotype was identified by three generation sequencing technology.The homologous modeling and molecular docking of cisAB01 glycosyltransferase were used to explore the structural changes of the glycosyltransferase after key amino acid mutations.Results The serological phenotype was AB.The gene sequencing showed that the genotype was cisAB.01/O.01.02.Homology modeling and molecular docking showed that p.Pro156Leu and p.Gly268Ala mutation of cisAB01 glycosyltransferase alter the spatial structure of the binding groove of catalytic active center.Conclusion The p.Pro156Leu and p.Gly268Ala mutation are key sites for the bifunctional activity of cisAB01 glycosyltransferase.
作者
夏悦昕
邵林楠
李宁
周世航
刘志远
XIA Yuexin;SHAO Linnan;LI Ning;ZHOU Shihang;LIU zhiyuan(Dalian Blood Center,Dalian 116000;Dalian Municipal Women and Children's Medical Center(Group),Dalian 116000)
出处
《临床输血与检验》
CAS
2024年第6期792-796,共5页
Journal of Clinical Transfusion and Laboratory Medicine
关键词
cisAB亚型
PacBio三代测序
同源建模
分子机制
分子对接
cisAB subtype
PacBio third-generation sequencing technology
Homology modeling
Molecular mechanism
Molecular docking
