ABO blood group A transferase and its codon 69 substitution enzymes synthesize FORS1 antigen of FORS blood group system.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 07 2019
04 07 2019
Historique:
received:
12
03
2019
accepted:
17
06
2019
entrez:
6
7
2019
pubmed:
6
7
2019
medline:
27
10
2020
Statut:
epublish
Résumé
Human histo-blood group A transferase (AT) catalyzes the biosynthesis of oligosaccharide A antigen important in blood transfusion and cell/tissue/organ transplantation. This enzyme may synthesize Forssman antigen (FORS1) of the FORS blood group system when exon 3 or 4 of the AT mRNA is deleted and/or the LeuGlyGly tripeptide at codons 266-268 of AT is replaced by GlyGlyAla. The Met69Ser/Thr substitutions also confer weak Forssman glycolipid synthase (FS) activity. In this study, we prepared the human AT derivative constructs containing any of the 20 amino acids at codon 69 with and without the GlyGlyAla substitution, transfected DNA to newly generated COS1(B3GALNT1 + A4GALT) cells expressing an enhanced level of globoside (Gb4), the FS acceptor substrate, and immunologically examined the FORS1 expression. Our results showed that all those substitution constructs at codon 69 exhibited FS activity. The combination with GlyGlyAla significantly increased the activity. The conserved methionine residue in the ABO, but not GBGT1, gene-encoded proteins may implicate its contribution to the separation of these genes in genetic evolution. Surprisingly, with increased Gb4 availability, the original human AT with the methionine residue at codon 69 was also demonstrated to synthesize FORS1, providing another molecular mechanism of FORS1 appearance in cancer of ordinary FORS1-negative individuals.
Identifiants
pubmed: 31273262
doi: 10.1038/s41598-019-46029-7
pii: 10.1038/s41598-019-46029-7
pmc: PMC6609624
doi:
Substances chimiques
ABO Blood-Group System
0
Antigens, Surface
0
Blood Group Antigens
0
Codon
0
antigen FORSE-1
0
Transferases
EC 2.-
GBGT1 protein, human
EC 2.4.1.-
N-Acetylgalactosaminyltransferases
EC 2.4.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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