Download MendeleyCrystal structure of the catalytic domain of Clostridium perfringens neuraminidase in complex with a non-carbohydrate-based inhibitor, 2-(cyclohexylamino)ethanesulfonic acid
Lee, Y., Youn, H.-S., Lee, J.-G., An, J.Y., Park, K.R., Kang, J.Y., Ryu, Y.B., Jin, M.S., Park, K.H., Eom, S.H.(2017) Biochem Biophys Res Commun 486: 470-475
- PubMed: 28315686
- DOI: https://doi.org/10.1016/j.bbrc.2017.03.064
- Primary Citation of Related Structures:
5TSP - PubMed Abstract:
Anti-bacterial and anti-viral neuraminidase agents inhibit neuraminidase activity catalyzing the hydrolysis of terminal N-acetylneuraminic acid (Neu5Ac) from glycoconjugates and help to prevent the host pathogenesis that lead to fatal infectious diseases including influenza, bacteremia, sepsis, and cholera. Emerging antibiotic and drug resistances to commonly used anti-neuraminidase agents such as oseltamivir (Tamiflu) and zanamivir (Relenza) have highlighted the need to develop new anti-neuraminidase drugs. We obtained a serendipitous complex crystal of the catalytic domain of Clostridium perfringens neuraminidase (CpNanI CD ) with 2-(cyclohexylamino)ethanesulfonic acid (CHES) as a buffer. Here, we report the crystal structure of CpNanI CD in complex with CHES at 1.24?? resolution. Amphipathic CHES binds to the catalytic site of CpNanI CD similar to the substrate (Neu5Ac) binding site. The 2-aminoethanesulfonic acid moiety and cyclohexyl groups of CHES interact with the cluster of three arginine residues and with the hydrophobic pocket of the CpNanI CD catalytic site. In addition, a structural comparison with other bacterial and human neuraminidases suggests that CHES could serve as a scaffold for the development of new anti-neuraminidase agents targeting CpNanI.
Organizational Affiliation:
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea; Steitz Center for Structural Biology, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
