8OG1

Exostosin-like 3 apo enzyme

8OG1 の概要

• エントリーDOI: 10.2210/pdb8og1/pdb
• 分子名称: Exostosin-like 3, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: glycosyltransferase, heparan sulfate, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 103313.56

構造登録者

Sammon, D.,Hohenester, E. (登録日: 2023-03-17, 公開日: 2023-07-12, 最終更新日: 2024-11-13)

主引用文献

Sammon, D.,Krueger, A.,Busse-Wicher, M.,Morgan, R.M.,Haslam, S.M.,Schumann, B.,Briggs, D.C.,Hohenester, E.
Molecular mechanism of decision-making in glycosaminoglycan biosynthesis.
Nat Commun, 14:6425-6425, 2023

PubMed Abstract: Two major glycosaminoglycan types, heparan sulfate (HS) and chondroitin sulfate (CS), control many aspects of development and physiology in a type-specific manner. HS and CS are attached to core proteins via a common linker tetrasaccharide, but differ in their polymer backbones. How core proteins are specifically modified with HS or CS has been an enduring mystery. By reconstituting glycosaminoglycan biosynthesis in vitro, we establish that the CS-initiating N-acetylgalactosaminyltransferase CSGALNACT2 modifies all glycopeptide substrates equally, whereas the HS-initiating N-acetylglucosaminyltransferase EXTL3 is selective. Structure-function analysis reveals that acidic residues in the glycopeptide substrate and a basic exosite in EXTL3 are critical for specifying HS biosynthesis. Linker phosphorylation by the xylose kinase FAM20B accelerates linker synthesis and initiation of both HS and CS, but has no effect on the subsequent polymerisation of the backbone. Our results demonstrate that modification with CS occurs by default and must be overridden by EXTL3 to produce HS.

PubMed: 37828045
DOI: 10.1038/s41467-023-42236-z

実験手法

X-RAY DIFFRACTION (1.58 Å)