8CD0

Human heparan sulfate N-deacetylase-N-sulfotransferase 1 in complex with calcium, 3'-phosphoadenosine-5'-phosphosulfate, and nanobody nAb7 (composite map and model)

8CD0 の概要

• エントリーDOI: 10.2210/pdb8cd0/pdb
• 関連するPDBエントリー: 1NST 8CD0
• EMDBエントリー: 16564 16565
• 分子名称: Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1, Nanobody nAb7, ADENOSINE-3'-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: deacetylase, sulfotransferase, heparan sulfate, carbohydrate, glycosaminoglycan, nanobody
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 119121.21

構造登録者

Mycroft-West, C.J.,Wu, L. (登録日: 2023-01-29, 公開日: 2024-02-07, 最終更新日: 2024-10-09)

主引用文献

Mycroft-West, C.J.,Abdelkarim, S.,Duyvesteyn, H.M.E.,Gandhi, N.S.,Skidmore, M.A.,Owens, R.J.,Wu, L.
Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1.
Nat Commun, 15:1326-1326, 2024

PubMed Abstract: Heparan sulfate (HS) polysaccharides are major constituents of the extracellular matrix, which are involved in myriad structural and signaling processes. Mature HS polysaccharides contain complex, non-templated patterns of sulfation and epimerization, which mediate interactions with diverse protein partners. Complex HS modifications form around initial clusters of glucosamine-N-sulfate (GlcNS) on nascent polysaccharide chains, but the mechanistic basis underpinning incorporation of GlcNS itself into HS remains unclear. Here, we determine cryo-electron microscopy structures of human N-deacetylase-N-sulfotransferase (NDST)1, the bifunctional enzyme primarily responsible for initial GlcNS modification of HS. Our structures reveal the architecture of both NDST1 deacetylase and sulfotransferase catalytic domains, alongside a non-catalytic N-terminal domain. The two catalytic domains of NDST1 adopt a distinct back-to-back topology that limits direct cooperativity. Binding analyses, aided by activity-modulating nanobodies, suggest that anchoring of the substrate at the sulfotransferase domain initiates the NDST1 catalytic cycle, providing a plausible mechanism for cooperativity despite spatial domain separation. Our data shed light on key determinants of NDST1 activity, and describe tools to probe NDST1 function in vitro and in vivo.

PubMed: 38351061
DOI: 10.1038/s41467-024-45419-4

実験手法

ELECTRON MICROSCOPY (2.42 Å)