9DR4

Crystal structure of bifunctional GlmU from Staphylococcus aureus NCTC 8325 complexed with UTP, CoA and Glc 1-P

これはPDB形式変換不可エントリーです。

9DR4 の概要

• エントリーDOI: 10.2210/pdb9dr4/pdb
• 関連するPDBエントリー: 9DQF
• 分子名称: Bifunctional protein GlmU, COENZYME A, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: uridyltransferase, acetyltransferase, transferase
• 由来する生物種: Staphylococcus aureus subsp. aureus NCTC 8325
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51258.89

構造登録者

Pederick, J.L.,Bruning, J.B. (登録日: 2024-09-25, 公開日: 2025-05-14)

主引用文献

Pederick, J.L.,Kumar, A.,Pukala, T.L.,Bruning, J.B.
Functional and structural characterization of Staphylococcus aureus N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) reveals a redox-sensitive acetyltransferase activity.
Protein Sci., 34:e70111-e70111, 2025

PubMed Abstract: The bifunctional enzyme N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) is a promising antibiotic drug target, as it facilitates the biosynthesis of uridine 5'-diphospho-N-acetylglucosamine, an essential precursor of cell wall constituents. We identified that Staphylococcus aureus GlmU (SaGlmU), which was previously targeted for inhibitor development, possesses a dual-cysteine variation (C379/C404) within the acetyltransferase active site. Enzyme assays performed under reducing and non-reducing conditions revealed that the acetyltransferase activity of SaGlmU is redox-sensitive, displaying ~15-fold lower turnover and ~3-fold higher K value for the acetyl CoA substrate under non-reducing conditions. This sensitivity was absent in a C379A SaGlmU mutant. Analysis of SaGlmU by mass spectrometry, x-ray crystallography, and in silico modeling support that C379 and C404 act as a reversible, redox-sensitive switch by forming a disulfide under non-reducing conditions that impedes acetyl CoA recognition and turnover. Therefore, we recommend that future in vitro screening and characterization of SaGlmU inhibitors consider both reducing and non-reducing conditions.

PubMed: 40143772
DOI: 10.1002/pro.70111

実験手法

X-RAY DIFFRACTION (1.85 Å)