Publications

• Expression cloning of Forssman glycolipid synthetase: a novel member of the histo-blood group ABO gene family.

  Haslam D.B., Baenziger J.U.

  A phenotypic cloning approach was used to isolate a canine cDNA encoding Forssman glycolipid synthetase (FS; UDP-GalNAc:globoside alpha-1,3-N-acetylgalactosaminyltransferase; EC 2.4.1.88). The deduced amino acid sequence of FS demonstrates extensive identity to three previously cloned glycosyltran ... >> More

  A phenotypic cloning approach was used to isolate a canine cDNA encoding Forssman glycolipid synthetase (FS; UDP-GalNAc:globoside alpha-1,3-N-acetylgalactosaminyltransferase; EC 2.4.1.88). The deduced amino acid sequence of FS demonstrates extensive identity to three previously cloned glycosyltransferases, including the enzymes responsible for synthesis of histo-blood group A and B antigens. These three enzymes, like FS, catalyze the addition of either N-acetylgalactosamine (GalNAc) or galactose (Gal) in alpha-1,3-linkage to their respective substrates. Despite the high degree of sequence similarity among the transferases, we demonstrate that the FS cDNA encodes an enzyme capable of synthesizing Forssman glycolipid, and demonstrates no GalNAc or Gal transferase activity when closely related substrates are examined. Thus, the FS cDNA is a novel member of the histo-blood group ABO gene family that encodes glycosyltransferases with related but distinct substrate specificity. Cloning of the FS cDNA will allow a detailed dissection of the roles Forssman glycolipid plays in cellular differentiation, development, and malignant transformation. << Less

  Proc. Natl. Acad. Sci. U.S.A. 93:10697-10702(1996) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Molecular modeling of glycosyltransferases involved in the biosynthesis of blood group A, blood group B, Forssman, and iGb3 antigens and their interaction with substrates.

  Heissigerova H., Breton C., Moravcova J., Imberty A.

  A terminal alpha1-3 linked Gal or GalNAc sugar residue is the common structure found in several oligosaccharide antigens, such as blood groups A and B, the xeno-antigen, the Forssman antigen, and the isogloboside 3 (iGb3) glycolipid. The enzymes involved in the addition of this residue display str ... >> More

  A terminal alpha1-3 linked Gal or GalNAc sugar residue is the common structure found in several oligosaccharide antigens, such as blood groups A and B, the xeno-antigen, the Forssman antigen, and the isogloboside 3 (iGb3) glycolipid. The enzymes involved in the addition of this residue display strong amino acid sequence similarities, suggesting a common fold. From a recently solved crystal structure of the bovine alpha3-galactosyltransferase complexed with UDP, homology modeling methods were used to build the four other enzymes of this family in their locked conformation. Nucleotide-sugars, the Mn2+ ion, and oligosaccharide acceptors were docked in the models. Nine different amino acid regions are involved in the substrate binding sites. After geometry optimization of the complexes and analysis of the predicted structures, the basis of the specificities can be rationalized. In the nucleotide-sugar binding site, the specificity between Gal or GalNAc transferase activity is due to the relative size of two clue amino acids. In the acceptor site, the presence of up to three tryptophan residues define the complexity of the oligosaccharide that can be specifically recognized. The modeling study helps in rationalizing the crystallographic data obtained in this family and provides insights on the basis of substrate and donor recognition. << Less

  Glycobiology 13:377-386(2003) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Characterization of the human Forssman synthetase gene: an evolving association between glycolipid synthesis and host-microbial interactions.

  Xu H., Storch T., Yu M., Elliott S.P., Haslam D.B.

  Differences in glycolipid expression between species contribute to the tropism of many infectious pathogens for their hosts. For example, we demonstrate that cultured human and monkey urinary epithelial cells fail to bind a canine Escherichia coli uropathogenic isolate; however, transfection of th ... >> More

  Differences in glycolipid expression between species contribute to the tropism of many infectious pathogens for their hosts. For example, we demonstrate that cultured human and monkey urinary epithelial cells fail to bind a canine Escherichia coli uropathogenic isolate; however, transfection of these cells with the canine Forssman synthetase (FS) cDNA enables abundant adherence by the same pathogen, indicating that addition of a single sugar residue to a glycolipid receptor has marked effects on microbial attachment. Given the contribution of glycolipids to host-microbial interactions, we sought to determine why human tissues do not express Forssman glycolipid. Query of the GenBank(TM) data base yielded a human sequence with high identity to the canine FS cDNA. Reverse transcription polymerase chain reaction and Northern blotting demonstrated the presence of FS mRNA in all tissues examined. A human FS cDNA was characterized, revealing identities with the canine FS gene of 86 and 83% at the nucleotide and predicted amino acid sequences, respectively. In contrast to the canine FS cDNA, transfection of COS-1 cells with the human FS cDNA resulted in no detectable FS enzyme activity. These results suggest that variability in glycolipid synthesis between species is an important determinant of microbial tropism. Evolutionary pressure from pathogenic organisms may have contributed to diversity in glycolipid expression among species. << Less

  J. Biol. Chem. 274:29390-29398(1999) [PubMed] [EuropePMC]

• Biosynthesis of Forssman hapten from globoside by alpha-N-acetylgalactosaminyltransferase of guinea pig tissues.

  Kijimoto S., Ishibashi T., Makita A.

  Biochem Biophys Res Commun 56:177-184(1974) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• ABO blood group A transferases catalyze the biosynthesis of FORS blood group FORS1 antigen upon deletion of exon 3 or 4.

  Yamamoto M., Cid E., Yamamoto F.

  Evolutionarily related <i>ABO</i> and <i>GBGT1</i> genes encode, respectively, A and B glycosyltransferases (AT and BT) and Forssman glycolipid synthase (FS), which catalyze the biosynthesis of A and B, and Forssman (FORS1) oligosaccharide antigens responsible for the ABO and FORS blood group syst ... >> More

  Evolutionarily related <i>ABO</i> and <i>GBGT1</i> genes encode, respectively, A and B glycosyltransferases (AT and BT) and Forssman glycolipid synthase (FS), which catalyze the biosynthesis of A and B, and Forssman (FORS1) oligosaccharide antigens responsible for the ABO and FORS blood group systems. Humans are a Forssman antigen-negative species; however, rare individuals with A_pae phenotype express FORS1 on their red blood cells. We previously demonstrated that the replacement of the LeuGlyGly tripeptide sequence at codons 266 to 268 of human AT with <i>GBGT1</i>-encoded FS-specific GlyGlyAla enabled the enzyme to produce FORS1 antigen, although the FS activity was weak. We searched for additional molecular mechanisms that might allow human AT to express FORS1. A variety of derivative expression constructs of human AT were prepared. DNA was transfected into COS1 (B3GALNT1) cells, and cell-surface expression of FORS1 was immunologically monitored. To our surprise, the deletion of exon 3 or 4, but not of exon 2 or 5, of human AT transcripts bestowed moderate FS activity, indicating that the A allele is inherently capable of producing a protein with FS activity. Because RNA splicing is frequently altered in cancer, this mechanism may explain, at least partially, the appearance of FORS1 in human cancer. Furthermore, strong FS activity was attained, in addition to AT and BT activities, by cointroducing 1 of those deletions and the GlyGlyAla substitution, possibly by the synergistic effects of altered intra-Golgi localization/conformation by the former and modified enzyme specificity by the latter. << Less

  Blood Adv 1:2756-2766(2017) [PubMed] [EuropePMC]