8QK1

Crystal structure of Trichuris suis beta-N-acetyl-D-hexosaminidase - HEX-2 in apo form

Summary for 8QK1

• Entry DOI: 10.2210/pdb8qk1/pdb
• Descriptor: beta-N-acetylhexosaminidase, ZINC ION (3 entities in total)
• Functional Keywords: hexosaminidase, enzyme, glycoside hydrolase family 20, hydrolase
• Biological source: Trichuris suis (pig whipworm)
• Total number of polymer chains: 1
• Total formula weight: 63334.60

Authors

Dutkiewicz, Z.,Varrot, A. (deposition date: 2023-09-14, release date: 2024-06-26, Last modification date: 2026-01-14)

Primary citation

Dutkiewicz, Z.,Varrot, A.,Breese, K.J.,Stubbs, K.A.,Nuschy, L.,Adduci, I.,Paschinger, K.,Wilson, I.B.H.
Bioinformatic, Enzymatic, and Structural Characterization of Trichuris suis Hexosaminidase HEX-2.
Biochemistry, 63:1941-1954, 2024

PubMed Abstract: 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 β-hexosaminidase subclade present only in the Dorylaimia. We have expressed one of these, HEX-2 from , a porcine parasite, and shown that it prefers an aryl β--acetylgalactosaminide . 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 α1,3-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 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 HEX-2 also possesses the key glutamate residue found in human hexosaminidases of either GH20 subfamily, including HEXD whose biological function remains elusive.

PubMed: 39058279
DOI: 10.1021/acs.biochem.4c00187

Experimental method

X-RAY DIFFRACTION (2.55 Å)