
HGSNAT는 리소좀 내부에서 아세틸-CoA로부터 아세틸기를 헤파란 황산염의 말단 α-D-글루코사민에 전달하는 필수적인 아세틸화 반응을 촉매한다. 이 연구에서는 HGSNAT-아세틸-CoA 복합체의 고해상도 구조를 제시하고, MPS IIIC를 유발하는 돌연변이의 분자적 기반을 밝혔다.


coremsg

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. Mutation-induced dysfunction in HGSNAT causes abnormal accumulation of HS within the lysosomes and leads to an autosomal recessive neurodegenerative lysosomal storage disorder called mucopolysaccharidosis IIIC (MPS IIIC). There are no approved drugs or treatment strategies to cure or manage the symptoms of, MPS IIIC. Here, we use cryo-electron microscopy (cryo-EM) to determine a high-resolution structure of the HGSNAT-acetyl-CoA complex, the first step in HGSNAT catalyzed acetyltransferase reaction. In addition, we map the known MPS IIIC mutations onto the structure and elucidate the molecular basis for mutation-induced HGSNAT dysfunction.

### Competing Interest Statement

The authors have declared no competing interest.

Structure of the human heparan-α-glucosaminide N-acetyltransferase (HGSNAT)

인간-헤파란-α-글루코사미드-n-아세틸트랜스퍼라제-hgsnat-구조


인간 헤파란-α-글루코사미드 N-아세틸트랜스퍼라제(HGSNAT) 구조
