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Biochem Biophys Res Commun. 2017 Apr 29;486(2):470-475. doi: 10.1016/j.bbrc.2017.03.064. Epub 2017 Mar 16.

Crystal structure of the catalytic domain of Clostridium perfringens neuraminidase in complex with a non-carbohydrate-based inhibitor, 2-(cyclohexylamino)ethanesulfonic acid.

Author information

1
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.
2
Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea.
3
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
4
Division of Applied Life Science (BK21 plus), IALS, Gyeongsang National University, Jinju 52828, Republic of Korea.
5
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; Department of Chemistry, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea. Electronic address: eom@gist.ac.kr.

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 (CpNanICD) with 2-(cyclohexylamino)ethanesulfonic acid (CHES) as a buffer. Here, we report the crystal structure of CpNanICD in complex with CHES at 1.24 Å resolution. Amphipathic CHES binds to the catalytic site of CpNanICD 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 CpNanICD 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.

KEYWORDS:

Anti-neuraminidase agents; CHES; Clostridium perfringens; Crystal structure; NanI; Neuraminidase

PMID:
28315686
DOI:
10.1016/j.bbrc.2017.03.064
[Indexed for MEDLINE]

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