Group B Erythrocytes Enzymatically Converted to Group O Survive Normally in A, B, and O Individuals

Goldstein, Jack; Siviglia, Geraldine; Hurst, Rosa; Lenny, Leslie L.; Reich, Lilian

doi:10.1126/science.6274021

Cited by 142 publications

(79 citation statements)

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“…Glycosidases are useful for remodeling glycan structures. They are widely used for structural determination of complex glycans, as therapeutics in enzyme replacement therapies of lysosomal storage diseases such as Fabry's disease (31), and they have potential use for the production of biomedical products such as universal RBCs (32) and xenotransplants such as pig cruciate ligaments (33). For the latter applications, it is important that the enzymes have restricted substrate specificity, have high specific activity, and work optimally under normal physiological conditions including at neutral pH.…”

Section: Discussionmentioning

confidence: 99%

Identification of a GH110 Subfamily of α1,3-Galactosidases

Liu

Yuan

Bennett

et al. 2008

Journal of Biological Chemistry

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In search of ␣-galactosidases with improved kinetic properties for removal of the immunodominant ␣1,3-linked galactose residues of blood group B antigens, we recently identified a novel prokaryotic family of ␣-galactosidases (CAZy GH110) with highly restricted substrate specificity and neutral pH optimum (Liu, Q. P., Sulzenbacher, G., Yuan, H., Bennett, E. P., Pietz, G., Saunders, K., Spence, J., Nudelman, E., Levery, S. B., White, T., Neveu, J. M., Lane, W. S., Bourne, Y., Olsson, M. L., Henrissat, B., and Clausen, H. (2007) Nat. Biotechnol. 25, 454 -464). One member of this family from Bacteroides fragilis had exquisite substrate specificity for the branched blood group B structure Gal␣1-3(Fuc␣1-2)Gal, whereas linear oligosaccharides terminated by ␣1,3-linked galactose such as the immunodominant xenotransplantation epitope Gal␣1-3Gal␤1-4GlcNAc did not serve as substrates. Here we demonstrate the existence of two distinct subfamilies of GH110 in B. fragilis and thetaiotaomicron strains. Members of one subfamily have exclusive specificity for the branched blood group B structures, whereas members of a newly identified subfamily represent linkage specific ␣1,3-galactosidases that act equally well on both branched blood group B and linear ␣1,3Gal structures. We determined by one-dimensional 1 H NMR spectroscopy that GH110 enzymes function with an inverting mechanism, which is in striking contrast to all other known ␣-galactosidases that use a retaining mechanism. The novel GH110 subfamily offers enzymes with highly improved performance in enzymatic removal of the immunodominant ␣3Gal xenotransplantation epitope.

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Section: Discussionmentioning

confidence: 99%

Identification of a GH110 Subfamily of α1,3-Galactosidases

Liu

Yuan

Bennett

et al. 2008

Journal of Biological Chemistry

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“…By using a specific exoglycosidase, this technique has been used successfully to cleave the B blood group antigen, allowing for the conversion of group B RBCs to group O before transfusion. 10,11 However, this general approach is limited by the availability of enzymes of the required specificities. Of the more than 200 known blood group antigens, B is the only antigen that has been specifically and effectively removed enzymatically.…”

Section: Introductionmentioning

confidence: 99%

Polyethylene glycol–coated red blood cells fail to bind glycophorin A–specific antibodies and are impervious to invasion by the Plasmodium falciparum malaria parasite

Blackall

Armstrong

Meiselman

et al. 2001

Blood

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IntroductionThe red blood cell (RBC) membrane is architecturally complex and is characterized by significant biochemical diversity. Protein-, lipoprotein-, glycoprotein-, and carbohydrate-rich structures play an important role in ensuring the physical integrity of the cell and carrying out its physiologic functions. 1 However, the presence of these diverse RBC-surface molecules can also have adverse consequences. Several of these structures carry defined polymorphic epitopes, recognized serologically as blood group antigens, which can stimulate alloimmune responses (alloimmunization) after red blood cell transfusion or pregnancy. A second exposure to the same antigen may lead to serious clinical consequences, including hemolytic transfusion reactions and hemolytic disease of the newborn. Alloimmunization is particularly problematic in patient groups who receive multiple transfusions. For example, up to 30% of chronically transfused patients with sickle cell disease become sensitized to one or more blood group antigens. 2 Aside from alloimmunization, a more recently recognized consequence of the presence of diverse molecules on the surface of RBCs is that microorganisms have adapted to use certain ones as "docking points" in the initiation of disease. As an example, parvovirus B19 (a prominent cause of pure red cell aplasia) homes to erythroid precursors in the marrow through an interaction with the P blood group antigen. 3 In addition, the Duffy and glycophorin A blood group glycoproteins have been shown to play important roles as receptors for human malaria parasites. 4 Plasmodium vivax has an absolute requirement for a Duffy protein interaction in order to successfully invade and parasitize human RBCs. Consequently, red cells of the Fy aϪbϪ phenotype are resistant to invasion. 5 Plasmodium falciparum malaria parasites use glycophorin A epitopes to achieve the efficient invasion of RBCs. 6 The essential biochemistry of the complex invasion process of this parasite is not as well understood as that for P vivax. However, the gene encoding an important glycophorin A binding ligand of P falciparum, EBA-175, has been cloned and is being intensively studied. [7][8][9] There are circumstances in which it would be desirable to remove some of the antigenic epitopes or potential binding sites from the RBC surface, either to prevent alloimmunization or make RBCs resistant to microbial attack. Enzymatic removal of specific protein or carbohydrate structures is one possible approach. By using a specific exoglycosidase, this technique has been used successfully to cleave the B blood group antigen, allowing for the conversion of group B RBCs to group O before transfusion. 10,11 However, this general approach is limited by the availability of enzymes of the required specificities. Of the more than 200 known blood group antigens, B is the only antigen that has been specifically and effectively removed enzymatically. Although other less-specific proteases and glycosidases will certainly remove many antigens, they will also compr...

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“…This enzyme has been attracting more and more attention because its potential biotechnological applications in many aspects, such as conversion of serological type (Goldstein et al 1982), improving the gelling property (McCleary & Neukom 1982), increasing the sucrose yield in the beet sugar industry (Yamane 1971), and eliminating raffinose-family oligosaccharides existing in the legume (Guimaraes et al 2001).…”

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confidence: 99%

Cloning and functional expression of α-galactosidase cDNA from Penicillium janczewskii zaleski

Zhang

Chen

et al. 2011

Biologia

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In recent years, α-galactosidase has been attracting more and more attention because of its potential applications in many aspects. Using reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends, a full-length cDNA sequence composed of 2,439 bp was cloned from Penicillium janczewskii zaleski and was subcloned into pPICZαA and transformed into Pichia pastoris strain X-33. In a 10-L fermentor, the recombinant yeast expressed α-galactosidase with a yield of 254 U/mL by methanol induction for 120 h. The recombinant enzyme showed the optimal activity at 40• C and pH 5.2. The Km values of the recombinant enzyme using p-nitrophenyl-α-D-galactopyranoside (pNPG), melibiose, raffinose and stachyose as substrates were 1, 16, 17.8 and 5.3 mM, respectively. Vmax values were 227.3, 116.7, 104.8, and 80.6 µM/min using pNPG, melibiose, raffinose and stachyose as substrates, respectively. The α-galactosidase exhibited no sensitivity to various metal ions and ethylenediaminetetraacetic acid, and hydrolyzed melibiose, raffinose and stachyose with different levels of galactose release. The biochemical characteristics of the α-galactosidase suggest that the enzyme may have a prospective application in feed industry as an additive.

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Group B Erythrocytes Enzymatically Converted to Group O Survive Normally in A, B, and O Individuals

Cited by 142 publications

References 6 publications

Identification of a GH110 Subfamily of α1,3-Galactosidases

Identification of a GH110 Subfamily of α1,3-Galactosidases

Polyethylene glycol–coated red blood cells fail to bind glycophorin A–specific antibodies and are impervious to invasion by the Plasmodium falciparum malaria parasite

Cloning and functional expression of α-galactosidase cDNA from Penicillium janczewskii zaleski

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