ePrints

NAG-thiazoline is a potent inhibitor of the Vibrio campbellii GH20 β-N-Acetylglucosaminidase

Lookup NU author(s): Dr David Bulmer, Professor Bert van den Berg

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

© 2020 Federation of European Biochemical Societies. 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 VhGlcNAcase from Vibrio campbellii (formerly V. harveyi) ATCC BAA-1116. NGT strongly inhibited VhGlcNAcase with an IC50 of 11.9 ± 1.0 μm and Ki 62 ± 3 µm, respectively. NGT was also found to completely inhibit the growth of V. campbellii strain 650 with an minimal inhibitory concentration value of 0.5 µm. ITC data analysis showed direct binding of NGT to VhGlcNAcase with a Kd of 32 ± 1.2 μm. The observed ΔG°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 VhGlcNAcase 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.

Publication metadata

Author(s): Meekrathok P, Stubbs KA, Aunkham A, Kaewmaneewat A, Kardkuntod A, Bulmer DM, van den Berg B, Suginta W

Publication type: Article

Publication status: Published

Journal: The FEBS Journal

Year: 2020

Volume: 287

Issue: 22

Pages: 4982-4995

Print publication date: 01/11/2020

Online publication date: 07/03/2020

Acceptance date: 04/03/2020

ISSN (print): 1742-464X

ISSN (electronic): 1742-4658

Publisher: John Wiley & Sons, Inc.

URL: https://doi.org/10.1111/febs.15283

DOI: 10.1111/febs.15283

PubMed id: 32145141

Altmetrics

Share