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Identification of a GH110 subfamily of alpha 1,3-galactosidases - Novel enzymes for removal of the alpha 3Gal xenotransplantation antigen

Liu, Qiyong P; Yuan, Huaiping; Bennett, Eric P; Levery, Steven B; Nudelman, Edward; Spence, Jean; Pietz, Greg; Saunders, Kristen; White, Thayer and Olsson, Martin L LU , et al. (2008) In Journal of Biological Chemistry 283(13). p.8545-8554
Abstract
In search of alpha-galactosidases with improved kinetic properties for removal of the immunodominant alpha 1,3-linked galactose residues of blood group B antigens, we recently identified a novel prokaryotic family of alpha-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 alpha 1-3(Fuc alpha 1-2) Gal, whereas... (More)
In search of alpha-galactosidases with improved kinetic properties for removal of the immunodominant alpha 1,3-linked galactose residues of blood group B antigens, we recently identified a novel prokaryotic family of alpha-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 alpha 1-3(Fuc alpha 1-2) Gal, whereas linear oligosaccharides terminated by alpha 1,3-linked galactose such as the immunodominant xenotransplantation epitope Gal alpha 1-3Gal beta 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 alpha 1,3-galactosidases that act equally well on both branched blood group B and linear alpha 1,3Gal structures. We determined by one-dimensional H-1 NMR spectroscopy that GH110 enzymes function with an inverting mechanism, which is in striking contrast to all other known alpha-galactosidases that use a retaining mechanism. The novel GH110 subfamily offers enzymes with highly improved performance in enzymatic removal of the immunodominant alpha 3Gal xenotransplantation epitope. (Less)
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Journal of Biological Chemistry
volume
283
issue
13
pages
8545 - 8554
publisher
ASBMB
external identifiers
  • wos:000254288000053
  • scopus:43749123693
ISSN
1083-351X
DOI
10.1074/jbc.M709020200
language
English
LU publication?
yes
id
26752e67-6d56-4094-a9a2-913354432d6b (old id 1185019)
date added to LUP
2008-09-02 14:57:22
date last changed
2017-05-21 03:32:29
@article{26752e67-6d56-4094-a9a2-913354432d6b,
  abstract     = {In search of alpha-galactosidases with improved kinetic properties for removal of the immunodominant alpha 1,3-linked galactose residues of blood group B antigens, we recently identified a novel prokaryotic family of alpha-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 alpha 1-3(Fuc alpha 1-2) Gal, whereas linear oligosaccharides terminated by alpha 1,3-linked galactose such as the immunodominant xenotransplantation epitope Gal alpha 1-3Gal beta 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 alpha 1,3-galactosidases that act equally well on both branched blood group B and linear alpha 1,3Gal structures. We determined by one-dimensional H-1 NMR spectroscopy that GH110 enzymes function with an inverting mechanism, which is in striking contrast to all other known alpha-galactosidases that use a retaining mechanism. The novel GH110 subfamily offers enzymes with highly improved performance in enzymatic removal of the immunodominant alpha 3Gal xenotransplantation epitope.},
  author       = {Liu, Qiyong P and Yuan, Huaiping and Bennett, Eric P and Levery, Steven B and Nudelman, Edward and Spence, Jean and Pietz, Greg and Saunders, Kristen and White, Thayer and Olsson, Martin L and Henrissat, Bernard and Sulzenbacher, Gerlind and Clausen, Henrik},
  issn         = {1083-351X},
  language     = {eng},
  number       = {13},
  pages        = {8545--8554},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Identification of a GH110 subfamily of alpha 1,3-galactosidases - Novel enzymes for removal of the alpha 3Gal xenotransplantation antigen},
  url          = {http://dx.doi.org/10.1074/jbc.M709020200},
  volume       = {283},
  year         = {2008},
}