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Title (en)
Bioinformatic, Enzymatic, and Structural Characterization of Trichuris suis Hexosaminidase HEX-2
Language
English
Description (en)
Hexosaminidases are key enzymes in glycoconjugate metabolism and occur in all kingdoms of life. Here, we have investigated the phylogeny of the GH20 glycosyl hydrolase family in nematodes and identified a ?-hexosaminidase subclade present only in the Dorylaimia. We have expressed one of these, HEX-2 from Trichuris suis, a porcine parasite, and shown that it prefers an aryl ?-N-acetylgalactosaminide in vitro. HEX-2 has an almost neutral pH optimum and is best inhibited by GalNAc-isofagomine. Toward N-glycan substrates, it displays a preference for the removal of GalNAc residues from LacdiNAc motifs as well as the GlcNAc attached to the ?1,3-linked core mannose. Therefore, it has a broader specificity than insect fused lobe (FDL) hexosaminidases but one narrower than distant homologues from plants. Its X-ray crystal structure, the first of any subfamily 1 GH20 hexosaminidase to be determined, is closest to Streptococcus pneumoniae GH20C and the active site is predicted to be compatible with accommodating both GalNAc and GlcNAc. The new structure extends our knowledge about this large enzyme family, particularly as T. suis HEX-2 also possesses the key glutamate residue found in human hexosaminidases of either GH20 subfamily, including HEXD whose biological function remains elusive.
Keywords (en)
Animals; Trichurisenzymology; Substrate Specificity; Computational Biology Methods; Crystallography, X-Ray; Amino Acid Sequence; Phylogeny; Models, Molecular; Hexosaminidases Chemistry Metabolism Genetics; Molecular Sequence Data; Catalytic Domain; Helminth Proteins Chemistry Metabolism Genetics; beta-N-Acetylhexosaminidases Metabolism Chemistry Genetics
DOI
10.1021/acs.biochem.4c00187
Author of the digital object
Zuzanna Dutkiewicz  (BOKU University)
Iain B. H. Wilson  (BOKU University)
Katharina Paschinger  (BOKU University)
Isabella Adduci  (University of Veterinary Medicine Vienna)
Lena Nuschy  (BOKU University)
Keith A. Stubbs  (University of Western Australia)
Annabelle Varrot  (Université Grenoble Alpes)
Karen J. Breese  (University of Western Australia)
Format
application/pdf
Size
10.6 MB
Licence Selected
CC BY 4.0 International
Type of publication
Article
Name of Publication (en)
Biochemistry
Pages or Volume
14
Volume
63
Number
15
From Page
1941
To Page
1954
Publisher
American Chemical Society
Publication Date
2024