8B63

Crystal Structure of P. aeruginosa WaaG in complex with UDP-GalNAc

8B63 の概要

• エントリーDOI: 10.2210/pdb8b63/pdb
• 分子名称: UDP-glucose:(Heptosyl) LPS alpha 1,3-glucosyltransferase WaaG, URIDINE-DIPHOSPHATE-N-ACETYLGALACTOSAMINE, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: glycosyltransferase, waag, transferase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 85060.71

構造登録者

Scaletti, E.,Gustafsson Westergren, R.,Stenmark, P. (登録日: 2022-09-25, 公開日: 2023-10-04, 最終更新日: 2024-04-17)

主引用文献

Scaletti, E.R.,Pettersson, P.,Patrick, J.,Shilling, P.J.,Westergren, R.G.,Daley, D.O.,Maler, L.,Widmalm, G.,Stenmark, P.
Structural and functional insights into the Pseudomonas aeruginosa glycosyltransferase WaaG and the implications for lipopolysaccharide biosynthesis.
J.Biol.Chem., 299:105256-105256, 2023

PubMed Abstract: The glycosyltransferase WaaG in Pseudomonas aeruginosa (PaWaaG) is involved in the synthesis of the core region of lipopolysaccharides. It is a promising target for developing adjuvants that could help in the uptake of antibiotics. Herein, we have determined structures of PaWaaG in complex with the nucleotide-sugars UDP-glucose, UDP-galactose, and UDP-GalNAc. Structural comparison with the homolog from Escherichia coli (EcWaaG) revealed five key differences in the sugar-binding pocket. Solution-state NMR analysis showed that WT PaWaaG specifically hydrolyzes UDP-GalNAc and unlike EcWaaG, does not hydrolyze UDP-glucose. Furthermore, we found that a PaWaaG mutant (Y97F/T208R/N282A/T283A/T285I) designed to resemble the EcWaaG sugar binding site, only hydrolyzed UDP-glucose, underscoring the importance of the identified amino acids in substrate specificity. However, neither WT PaWaaG nor the PaWaaG mutant capable of hydrolyzing UDP-glucose was able to complement an E. coli ΔwaaG strain, indicating that more remains to be uncovered about the function of PaWaaG in vivo. This structural and biochemical information will guide future structure-based drug design efforts targeting PaWaaG.

PubMed: 37716703
DOI: 10.1016/j.jbc.2023.105256

実験手法

X-RAY DIFFRACTION (2.2 Å)