Identification of the cisAB (c. 796A>C) allele and molecular docking of its transferase
10.13303/j.cjbt.issn.1004-549x.2025.10.015
- VernacularTitle:cisAB（c. 796A>C）等位基因鉴定及其转移酶的分子对接
- Author:
Yongkui KONG
1
;
Shuya WANG
1
;
Huifang JIN
1
;
Jing WANG
1
;
Lu ZHENG
1
;
Yanjie GONG
2
;
Qiankun YANG
1
Author Information
1. Department of Blood Transfusion, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
2. Department of Blood Transfusion, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- Publication Type:Journal Article
- Keywords:
ABO subtype;
genotype;
pedigree analysis;
homology modeling;
molecular docking
- From:
Chinese Journal of Blood Transfusion
2025;38(10):1395-1402
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To reveal the molecular basis of the cisAB (p. Met266Leu) glycosyltransferase by studying a proband with cisAB subtype and his family. Methods: A male newborn was selected as the research subject. Tube methods were used to identify ABO blood types of the proband and his family members. PCR-SSP detection, ABO gene sequencing, and cloning analysis were performed on the proband and some family members. The inheritance pattern of the subtype gene in the family was determined through pedigree analysis. Homology modeling was used to analyze the impact of amino acid variations on the structure of the transferase, and molecular docking was used to demonstrate the bifunctional activity of the transferase and the donor-receptor binding conformation. Results: Serological tests showed that the proband and his father had enhanced anti-H agglutination, and the grandmother had a forward and reverse discrepancy. Sequencing of the proband revealed heterozygous variations of c. 297A>G, c. 526C>G, c. 657C>T, c. 703G>A, c. 803G>C, and c. 930G>A compared with A1. 01 (compared with B. 01, lacking the c. 796C>A variation, namely harboring the c. 796A>C variation) and c. 261delG. Combined with cloning analysis, the proband's genotype was determined to be ABO
cisAB (c. 796A>C)/ABO
O. 01. 01, the father's genotype was ABO
cisAB (c. 796A>C)/ABO
O. 01. 02, and the grandmother's genotype was ABO
cisAB (c. 796A>C)/ABO
B102. Pedigree analysis indicated that the cisAB allele in this newborn was inherited from his father and grandmother rather than a natural mutation. Homology modeling showed that the side chain orientation and intermolecular forces of Leu266 in the cisAB (p. Met266Leu) transferase changed, and molecular docking demonstrated that the "binding pocket" of the active center of the variant enzyme could accommodate both UDP-GalNAc and UDP-Gal, indicating that the cisAB enzyme structure has bifunctional activity. Conclusion: The bifunctional activity of this cisAB (p. Met266Leu) enzyme is related to the nucleotide variation of c. 796A>C, and molecular docking indicates that the enzyme has dual affinity for A/B sugar donors.
