Structure of the human heparan-α-glucosaminide N-acetyltransferase (HGSNAT)
elifesciences.org
Degradation of heparan sulfate (HS), a glycosaminoglycan (GAG) comprised of repeating units of N-acetylglucosamine and glucuronic acid, begins in the cytosol and is completed in the lysosomes Acetylation of the terminal non-reducing amino group of α-D-glucosamine of HS is essential for its complete
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- Degradation of heparan sulfate (HS), a glycosaminoglycan (GAG) comprised of repeating units of N-acetylglucosamine and glucuronic acid, begins in the cytosol and is completed in the lysosomes
- Acetylation of the terminal non-reducing amino group of α-D-glucosamine of HS is essential for its complete breakdown into monosaccharides and free sulfate.
- Heparan-α-glucosaminide N-acetyltransferase (HGSNAT), a resident of the lysosomal membrane, catalyzes this essential acetylation reaction by accepting and transferring the acetyl group from cytosolic acetyl-CoA to terminal α-D-glucosamine of HS in the lysosomal lumen.
- dysfunction in HGSNAT causes abnormal accumulation of HS within the lysosomes
- The localization of HGSNAT happens via the adaptor protein-mediated pathway, aided by the lysosomal targeting motifs [DE]-XXXL[LI] (204ETDRLI209) and YXXØ (624YILYRKK630) present towards the N- and C-terminus of HGSNAT respectively
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