5LY7

Crystal structure of NagZ H174A mutant from Pseudomonas aeruginosa in complex with the inhibitor 2-acetamido-1,2-dideoxynojirimycin

5LY7 の概要

• エントリーDOI: 10.2210/pdb5ly7/pdb
• 分子名称: Beta-hexosaminidase, DI(HYDROXYETHYL)ETHER, 2-ACETAMIDO-1,2-DIDEOXYNOJIRMYCIN, ... (4 entities in total)
• 機能のキーワード: cell-wall recycling beta-hexosaminidase pseudomonas aeruginosa inhibitor, gene regulation
• 由来する生物種: Pseudomonas aeruginosa
• 細胞内の位置: Cytoplasm : Q9HZK0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77121.90

構造登録者

Acebron, I.,Artola-Recolons, C.,Mahasenan, K.,Mobashery, S.,Hermoso, J.A. (登録日: 2016-09-25, 公開日: 2017-05-17, 最終更新日: 2024-05-01)

主引用文献

Acebron, I.,Mahasenan, K.V.,De Benedetti, S.,Lee, M.,Artola-Recolons, C.,Hesek, D.,Wang, H.,Hermoso, J.A.,Mobashery, S.
Catalytic Cycle of the N-Acetylglucosaminidase NagZ from Pseudomonas aeruginosa.
J. Am. Chem. Soc., 139:6795-6798, 2017

PubMed Abstract: The N-acetylglucosaminidase NagZ of Pseudomonas aeruginosa catalyzes the first cytoplasmic step in recycling of muropeptides, cell-wall-derived natural products. This reaction regulates gene expression for the β-lactam resistance enzyme, β-lactamase. The enzyme catalyzes hydrolysis of N-acetyl-β-d-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-d-muramyl-peptide (1) to N-acetyl-β-d-glucosamine (2) and 1,6-anhydro-N-acetyl-β-d-muramyl-peptide (3). The structural and functional aspects of catalysis by NagZ were investigated by a total of seven X-ray structures, three computational models based on the X-ray structures, molecular-dynamics simulations and mutagenesis. The structural insights came from the unbound state and complexes of NagZ with the substrate, products and a mimetic of the transient oxocarbenium species, which were prepared by synthesis. The mechanism involves a histidine as acid/base catalyst, which is unique for glycosidases. The turnover process utilizes covalent modification of D244, requiring two transition-state species and is regulated by coordination with a zinc ion. The analysis provides a seamless continuum for the catalytic cycle, incorporating large motions by four loops that surround the active site.

PubMed: 28482153
DOI: 10.1021/jacs.7b01626

実験手法

X-RAY DIFFRACTION (3.1 Å)