Skip to Main content Skip to Navigation
Journal articles

Identification of a GH110 Subfamily of ␣1,3-Galactosidases: NOVEL ENZYMES FOR REMOVAL OF THE ␣3GAL XENOTRANSPLANTATION ANTIGEN

Abstract : In search of α-galactosidases with improved kinetic properties for removal of the immunodominant α1,3-linked galactose residues of blood group B antigens, we recently identified a novel prokaryotic family of α-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 Galα1–3(Fucα1–2)Gal, whereas linear oligosaccharides terminated by α1,3-linked galactose such as the immunodominant xenotransplantation epitope Galα1–3Galβ1–4GlcNAc 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 α1,3-galactosidases that act equally well on both branched blood group B and linear α1,3Gal structures. We determined by one-dimensional 1H NMR spectroscopy that GH110 enzymes function with an inverting mechanism, which is in striking contrast to all other known α-galactosidases that use a retaining mechanism. The novel GH110 subfamily offers enzymes with highly improved performance in enzymatic removal of the immunodominant α3Gal xenotransplantation epitope.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03160511
Contributor : Gerlind Sulzenbacher Connect in order to contact the contributor
Submitted on : Friday, March 5, 2021 - 11:49:23 AM
Last modification on : Wednesday, January 5, 2022 - 12:26:02 PM
Long-term archiving on: : Sunday, June 6, 2021 - 6:39:46 PM

File

GH110.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Qiyong P Liu, Huaiping yuan, Eric P Bennett, Steven B Levery, Edward Nudelman, et al.. Identification of a GH110 Subfamily of ␣1,3-Galactosidases: NOVEL ENZYMES FOR REMOVAL OF THE ␣3GAL XENOTRANSPLANTATION ANTIGEN. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (13), pp.8545-8554. ⟨10.1074/jbc.M709020200⟩. ⟨hal-03160511⟩

Share

Metrics

Record views

3

Files downloads

18