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NAG‐thiazoline is a potent inhibitor of the Vibrio campbellii GH20 β‐ N ‐Acetylglucosaminidase
Author(s) -
Meekrathok Piyanat,
Stubbs Keith A.,
Aunkham Anuwat,
Kaewmaneewat Anuphon,
Kardkuntod Apinya,
Bulmer David M.,
Berg Bert,
Suginta Wipa
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15283
Subject(s) - protein data bank (rcsb pdb) , vibrio , chitin , vibrio harveyi , biology , microbiology and biotechnology , hydrogen bond , bacteria , stereochemistry , biochemistry , chemistry , genetics , molecule , chitosan , organic chemistry
Vibrio spp. play a vital role in the recycling of chitin in oceans, but several Vibrio strains are highly infectious to aquatic animals and humans. These bacteria require chitin for growth; thus, potent inhibitors of chitin‐degrading enzymes could serve as candidate drugs against Vibrio infections. This study examined NAG‐thiazoline (NGT)‐mediated inhibition of a recombinantly expressed GH20 β‐ N ‐acetylglucosaminidase, namely Vh GlcNAcase from Vibrio campbellii (formerly V. harveyi ) ATCC BAA‐1116. NGT strongly inhibited Vh GlcNAcase with an IC 50 of 11.9 ± 1.0 μ m and K i 62 ± 3 µ m , respectively. NGT was also found to completely inhibit the growth of V. campbellii strain 650 with an minimal inhibitory concentration value of 0.5 µ m . ITC data analysis showed direct binding of NGT to Vh GlcNAcase with a K d of 32 ± 1.2 μ m . The observed Δ G ° binding of −7.56 kcal·mol −1 is the result of a large negative enthalpy change and a small positive entropic compensation, suggesting that NGT binding is enthalpy‐driven. The structural complex shows that NGT fully occupies the substrate‐binding pocket of Vh GlcNAcase and makes an exclusive hydrogen bond network, as well as hydrophobic interactions with the conserved residues around the −1 subsite. Our results strongly suggest that NGT could serve as an excellent scaffold for further development of antimicrobial agents against Vibrio infections. Database Structural data are available in PDB database under the accession number 6K35 .