5TSP

Crystal structure of the catalytic domain of Clostridium perfringens neuraminidase (NanI) in complex with a CHES

Summary for 5TSP

• Entry DOI: 10.2210/pdb5tsp/pdb
• Descriptor: Sialidase, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: neuraminidase, hydrolase
• Biological source: Clostridium perfringens ATCC 13124
• Total number of polymer chains: 2
• Total formula weight: 103715.10

Authors

Lee, Y.,Youn, H.-S.,Lee, J.-G.,An, J.Y.,Park, K.R.,Kang, J.Y.,Jin, M.S.,Ryu, Y.B.,Park, K.H.,Eom, S.H. (deposition date: 2016-10-31, release date: 2017-03-29, Last modification date: 2023-11-08)

Primary citation

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.
Crystal structure of the catalytic domain of Clostridium perfringens neuraminidase in complex with a non-carbohydrate-based inhibitor, 2-(cyclohexylamino)ethanesulfonic acid
Biochem. Biophys. Res. Commun., 486:470-475, 2017

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

PubMed: 28315686
DOI: 10.1016/j.bbrc.2017.03.064

Experimental method

X-RAY DIFFRACTION (1.24 Å)