5NC9

Crystal structure of the polysaccharide deacetylase Bc1974 from Bacillus cereus in complex with (2S)-2,6-diamino-N-hydroxyhexanamide

Summary for 5NC9

• Entry DOI: 10.2210/pdb5nc9/pdb
• Descriptor: Peptidoglycan N-acetylglucosamine deacetylase, (2~{S})-2,6-bis(azanyl)-~{N}-oxidanyl-hexanamide, ZINC ION, ... (7 entities in total)
• Functional Keywords: ce4 domain, polysaccharide deacetylase, pgda, bacillus cereus, hydrolase, hydroxamate ligand
• Biological source: Bacillus cereus ATCC 14579; More
• Total number of polymer chains: 4
• Total formula weight: 112849.50

Authors

Giastas, P.,Andreou, A.,Eliopoulos, E.E. (deposition date: 2017-03-03, release date: 2018-02-21, Last modification date: 2024-05-08)

Primary citation

Giastas, P.,Andreou, A.,Papakyriakou, A.,Koutsioulis, D.,Balomenou, S.,Tzartos, S.J.,Bouriotis, V.,Eliopoulos, E.E.
Structures of the Peptidoglycan N-Acetylglucosamine Deacetylase Bc1974 and Its Complexes with Zinc Metalloenzyme Inhibitors.
Biochemistry, 57:753-763, 2018

PubMed Abstract: The cell wall peptidoglycan is recognized as a primary target of the innate immune system, and usually its disintegration results in bacterial lysis. Bacillus cereus, a close relative of the highly virulent Bacillus anthracis, contains 10 polysaccharide deacetylases. Among these, the peptidoglycan N-acetylglucosamine deacetylase Bc1974 is the highest homologue to the Bacillus anthracis Ba1977 that is required for full virulence and is involved in resistance to the host's lysozyme. These metalloenzymes belong to the carbohydrate esterase family 4 (CE4) and are attractive targets for the development of new anti-infective agents. Herein we report the first X-ray crystal structures of the NodB domain of Bc1974, the conserved catalytic core of CE4s, in the unliganded form and in complex with four known metalloenzyme inhibitors and two amino acid hydroxamates that target the active site metal. These structures revealed the presence of two conformational states of a catalytic loop known as motif-4 (MT4), which were not observed previously for peptidoglycan deacetylases, but were recently shown in the structure of a Vibrio clolerae chitin deacetylase. By employing molecular docking of a substrate model, we describe a catalytic mechanism that probably involves initial binding of the substrate in a receptive, more open state of MT4 and optimal catalytic activity in the closed state of MT4, consistent with the previous observations. The ligand-bound structures presented here, in addition to the five Bc1974 inhibitors identified, provide a valuable basis for the design of antibacterial agents that target the peptidoglycan deacetylase Ba1977.

PubMed: 29257674
DOI: 10.1021/acs.biochem.7b00919

Experimental method

X-RAY DIFFRACTION (2.44 Å)