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

Autor: Jung-Gyu Lee, Ki Hun Park, Young Bae Ryu, Kyoung Ryoung Park, Hyung-Seop Youn, Youngjin Lee, Jun Yop An, Soo Hyun Eom, Mi Sun Jin, Jung Youn Kang
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Models
Molecular
NanI
Glycoconjugate
Clostridium perfringens
Taurine
Amino Acid Motifs
Gene Expression
medicine.disease_cause
Crystallography
X-Ray
Biochemistry
Protein Structure
Secondary
RMSD
root mean square deviation
chemistry.chemical_compound
CHES
2-(cyclohexylamino)ethanesulfonic acid
Catalytic Domain
Cloning
Molecular
Enzyme Inhibitors
chemistry.chemical_classification
biology
CHES
Recombinant Proteins
medicine.drug
Oseltamivir
CpNanI
Clostridium perfringens neuraminidase NanI
Biophysics
Neuraminidase
Article
03 medical and health sciences
Zanamivir
Bacterial Proteins
Protein Domains
Hydrolase
medicine
Escherichia coli
Binding site
Molecular Biology
030102 biochemistry & molecular biology
Crystal structure
Anti-neuraminidase agents
Cell Biology
Neu5Ac
N-acetylneuraminic acid
SpNanB
Streptococcus pneumoniae NanB
030104 developmental biology
chemistry
Structural Homology
Protein
biology.protein
Ethanesulfonic acid
Zdroj: Biochemical and Biophysical Research Communications
ISSN: 1090-2104
0006-291X
Popis: 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.
Graphical abstract Image 1
Highlights • We determined the crystal structure of CpNanI bound to CHES at 1.24 Å resolution. • CHES binds to the catalytic site of CpNanI similar to the substrate binding site. • We suggest strategies for modification of CHES for the development of anti-CpNanI agents.
Databáze: OpenAIRE
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