5G5K

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

Summary for 5G5K

• Entry DOI: 10.2210/pdb5g5k/pdb
• Descriptor: BETA-HEXOSAMINIDASE, 2-ACETAMIDO-1,2-DIDEOXYNOJIRMYCIN (3 entities in total)
• Functional Keywords: hydrolase, cell-wall recycling, antibiotic resistance, glycoside hydrolase, n-acetylglucosaminidase, beta-hexosaminidase, inhibition, peptidoglycan
• Biological source: PSEUDOMONAS AERUGINOSA
• Cellular location: Cytoplasm : Q9HZK0
• Total number of polymer chains: 2
• Total formula weight: 77043.79

Authors

Acebron, I.,Artola-Recolons, C.,Mahasenan, K.,Mobashery, S.,Hermoso, J.A. (deposition date: 2016-05-25, release date: 2017-05-17, Last modification date: 2024-05-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.1 Å)