A novel <i>cis‐AB</i> variant allele arising from a nucleotide substitution A796C in the <i>B</i> transferase gene

Mifsud, Nicole A.; Watt, Julie M.; Condon, Jenny; Haddad, Albert P.; Sparrow, Rosemary L.

doi:10.1046/j.1537-2995.2000.40101276.x

Cited by 34 publications

(29 citation statements)

References 7 publications

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“…Several natural and recombinant cis-AB enzymes have been characterized with interchanges in the four amino acids such as AAAB (Arg-176, Gly-235, Leu-266, and Ala-268) (8), ABBA, AABA and BBBA, and BABA. Two other cis-AB enzymes result from point mutations of GTB: one at codon 266 (M266L) (9) and one at position 234 (P234S) (10). Another mutation at position 234 (P234A) has been reported to modify the specificity of the GTB to transfer not only Gal but also small amounts of GalNAc leading to a phenotype called B(A) (11).…”

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confidence: 99%

A Single Point Mutation Reverses the Donor Specificity of Human Blood Group B-synthesizing Galactosyltransferase

Marcus

Polakowski

Seto

et al. 2003

Journal of Biological Chemistry

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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 ␣1-3 galactosyltransferase (GTB) that transfers galactose from UDP-Gal to type 1 or type 2, ␣Fuc132␤Gal-R (H)-terminating acceptors. Similarly the A antigen is produced by an ␣1-3 N-acetylgalactosaminyltransferase that transfers N-acetylgalactosamine from UDP-GalNAc to H-acceptors. Human ␣1-3 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 novel cis-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.

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confidence: 99%

A Single Point Mutation Reverses the Donor Specificity of Human Blood Group B-synthesizing Galactosyltransferase

Marcus

Polakowski

Seto

et al. 2003

Journal of Biological Chemistry

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“…The cis-AB02 gene has a mutation on the B allele (B101) background that causes the single amino acid substitution M266L, 3) whereas cis-AB04 has a mutation on the A allele (A102) background causing L266M. 4) Additionally, cis-AB03 carrying the P234S mutation on B101 has also been found.…”

Section: Discussionmentioning

confidence: 99%

“…The L266M mutation, which is one of four mismatching residues between the A-and B-transferases, is also one of the candidate key residues determining substrate specificity, because it is also found in two cis-AB alleles, cis-AB02 and cis-AB04. 3,4) The important role of the 266th residue in substrate specificity has been confirmed by enzyme kinetic analysis using purified recombinant hybrid A/B-transferases. 5) Additionally, the P234S mutation been identified only in cis-AB03 as a single point mutation in B-transferase, suggesting that it allows B-transferase to acquire AB-transferase activity, according to genotyping and analysis of peripheral red blood cells.…”

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confidence: 90%

B-Transferase with a Pro234Ser Substitution Acquires AB-Transferase Activity

Nishida

Tanaka

Nishiyama

et al. 2011

Bioscience, Biotechnology, and Biochemistry

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“…Seven known B(A) or cisAB alleles exhibit mutations affecting these three amino acid residues (Gly235Ser, Leu266Met, Gly268Ala) or its neighbors (nt 700), all of which have been shown to be critical for the specificity of the transferase. CisAB02 involves different nonsynonymous substitutions of A796C on the B101 allele background and is typed as BBAB (Mifsud et al 2000). cisAB03 was typed as BBBB and is found at the nt 700 position; this mutation C > T) was found in a French family (Roubinet et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a novel B(A) allele with BBBA type at the ABO blood group

Deng

Wang

et al. 2006

J Hum Genet

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The ABO blood group is one of the main blood group systems, and it plays an important role in transfusion medicine and transplantation. To date, most of the many ABO subgroups with a weak expression of the A or B antigen on red blood cells have been elucidated to have specific molecular genetic background with respect to the ABO gene. The ABO*B(A) allele or CisAB allele is a type of dual ABO allele which can encode glycosyltransferases responsible for the conversion of H substance to both A and B antigen. We report here our characterization of a novel B(A) allele which differs from those reported previously.

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A novel cis‐AB variant allele arising from a nucleotide substitution A796C in the B transferase gene

Cited by 34 publications

References 7 publications

A Single Point Mutation Reverses the Donor Specificity of Human Blood Group B-synthesizing Galactosyltransferase

A Single Point Mutation Reverses the Donor Specificity of Human Blood Group B-synthesizing Galactosyltransferase

B-Transferase with a Pro234Ser Substitution Acquires AB-Transferase Activity

Characterization of a novel B(A) allele with BBBA type at the ABO blood group

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