6WMO

Human poly-N-acetyl-lactosamine synthase structure demonstrates a modular assembly of catalytic subsites for GT-A glycosyltransferases

6WMO の概要

• エントリーDOI: 10.2210/pdb6wmo/pdb
• 関連するPDBエントリー: 6WMM 6WMN
• 分子名称: N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: glycosyltransferase, gt-a fold, poly lacnac synthesis, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 88951.75

構造登録者

Kadirvelraj, R.,Wood, Z.A. (登録日: 2020-04-21, 公開日: 2020-12-02, 最終更新日: 2024-10-23)

主引用文献

Kadirvelraj, R.,Yang, J.Y.,Kim, H.W.,Sanders, J.H.,Moremen, K.W.,Wood, Z.A.
Comparison of human poly-N-acetyl-lactosamine synthase structure with GT-A fold glycosyltransferases supports a modular assembly of catalytic subsites.
J.Biol.Chem., 296:100110-100110, 2020

PubMed Abstract: Poly-N-acetyl-lactosamine (poly-LacNAc) structures are composed of repeating [-Galβ(1,4)-GlcNAcβ(1,3)-] glycan extensions. They are found on both N- and O-glycoproteins and glycolipids and play an important role in development, immune function, and human disease. The majority of mammalian poly-LacNAc is synthesized by the alternating iterative action of β1,3-N-acetylglucosaminyltransferase 2 (B3GNT2) and β1,4-galactosyltransferases. B3GNT2 is in the largest mammalian glycosyltransferase family, GT31, but little is known about the structure, substrate recognition, or catalysis by family members. Here we report the structures of human B3GNT2 in complex with UDP:Mg and in complex with both UDP:Mg and a glycan acceptor, lacto-N-neotetraose. The B3GNT2 structure conserves the GT-A fold and the DxD motif that coordinates a Mg ion for binding the UDP-GlcNAc sugar donor. The acceptor complex shows interactions with only the terminal Galβ(1,4)-GlcNAcβ(1,3)- disaccharide unit, which likely explains the specificity for both N- and O-glycan acceptors. Modeling of the UDP-GlcNAc donor supports a direct displacement inverting catalytic mechanism. Comparative structural analysis indicates that nucleotide sugar donors for GT-A fold glycosyltransferases bind in similar positions and conformations without conserving interacting residues, even for enzymes that use the same donor substrate. In contrast, the B3GNT2 acceptor binding site is consistent with prior models suggesting that the evolution of acceptor specificity involves loops inserted into the stable GT-A fold. These observations support the hypothesis that GT-A fold glycosyltransferases employ coevolving donor, acceptor, and catalytic subsite modules as templates to achieve the complex diversity of glycan linkages in biological systems.

PubMed: 33229435
DOI: 10.1074/jbc.RA120.015305

実験手法

X-RAY DIFFRACTION (1.85 Å)