title: The p.R168Q mutation is associated with the Bw phenotype and a predicted decrease in the stability of the resulting ABO glycosyltransferase.
abstract: BACKGROUND
  Mutation of ABO glycosyltransferase (GT) can cause protein stability changes that can result in a weak ABO phenotype. To explain the Bw phenotype of a novel ABO*Bw allele, a protein stability of the mutant GT, which enhances the information of the three-dimensional (3D) structural analysis, was calculated.
  
  
  METHODS
  ABO serology and genotyping were performed on a neonate and her five family members. A 3D structural analysis of the wild-type GTB and enzymes with a variety of mutations at Residue 168, along with predicted protein stability changes (ΔΔG) and flow cytometric analysis of ABO antigen expression on HeLa cells transfected with plasmids containing R168Q, R168L, and R168P mutants was also performed.
  
  
  RESULTS
  A novel ABO*Bw allele (c.503G>A, p.R168Q) was discovered. The structural analysis of 3D homology modeling predicted reduced protein stability of the mutant GTB, and the ΔΔG values, which inversely correlated with the mean relative fluorescence intensity of ABO antigen expression, quantitatively explained the reduced ABO antigen expression.
  
  
  CONCLUSIONS
  The predicted protein stability change of a mutant GT enzyme might be a useful and convenient approach to objectively and quantitatively explain the reduced ABO antigen expression.
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Seung Yeob
authors.initials: SY
authors.lastname: Lee
authors.forename: Chunhwa
authors.initials: C
authors.lastname: Ihm
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Shin
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Mark Harris
authors.initials: MH
authors.lastname: Yazer
authors.forename: Seung Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Myung Geun
authors.initials: MG
authors.lastname: Shin
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Shin
authors.forename: Soon Pal
authors.initials: SP
authors.lastname: Suh
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Ryang
authors.forename: Duck
authors.initials: D
authors.lastname: Cho
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D004795:Enzyme Stability; D005838:Genotype; D016695:Glycosyltransferases / Q000737:chemistry / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010641:Phenotype
chemical_list: D000017:ABO Blood-Group System; D016695:Glycosyltransferases