| DOI | Resolve DOI: https://doi.org/10.1074/jbc.M212002200 |
|---|
| Author | Search for: Marcus, Sandra L.; Search for: Polakowski, Robert; Search for: Seto, Nina O. L.1; Search for: Leinala, Eeva; Search for: Borisova, Svetana; Search for: Blancher, Antoine; Search for: Roubinet, Francis; Search for: Evans, Stephen V.; Search for: Palcic, Monica M. |
|---|
| Affiliation | - National Research Council of Canada. NRC Institute for Biological Sciences
|
|---|
| Format | Text, Article |
|---|
| Abstract | Blood group A and B antigens are carbohydrate structures that are synthesized by glycosyltransferase enzymes. The final step in B antigen synthesis is carried out by an α1–3 galactosyltransferase (GTB) that transfers galactose from UDP-Gal to type 1 or type 2, αFuc1→2βGal-R (H)-terminating acceptors. Similarly the A antigen is produced by an α1–3N-acetylgalactosaminyltransferase that transfersN-acetylgalactosamine from UDP-GalNAc to H-acceptors. Human α1–3 N-acetylgalactosaminyltransferase and GTB are highly homologous enzymes differing in only four of 354 amino acids (R176G, G235S, L266M, and G268A). Single crystal x-ray diffraction studies have shown that the latter two of these amino acids are responsible for the difference in donor specificity, while the other residues have roles in acceptor binding and turnover. Recently a novelcis-AB allele was discovered that produced A and B cell surface structures. It had codons corresponding to GTB with a single point mutation that replaced the conserved amino acid proline 234 with serine. Active enzyme expressed from a synthetic gene corresponding to GTB with a P234S mutation shows a dramatic and complete reversal of donor specificity. Although this enzyme contains all four “critical” amino acids associated with the production of blood group B antigen, it preferentially utilizes the blood group A donor UDP-GalNAc and shows only marginal transfer of UDP-Gal. The crystal structure of the mutant reveals the basis for the shift in donor specificity. |
|---|
| Publication date | 2003-04-04 |
|---|
| Publisher | American Society for Biochemistry and Molecular Biology |
|---|
| In | |
|---|
| Language | English |
|---|
| Peer reviewed | Yes |
|---|
| NRC number | MARCUS2003 |
|---|
| NPARC number | 9360243 |
|---|
| Export citation | Export as RIS |
|---|
| Report a correction | Report a correction (opens in a new tab) |
|---|
| Record identifier | d29cce49-e3d7-4121-b1aa-54e794fa6f20 |
|---|
| Record created | 2009-07-10 |
|---|
| Record modified | 2020-04-02 |
|---|
