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Kinetic, thermodynamic and structural analysis of tamiphosphor binding to neuraminidase of H1N1 (2009) pandemic influenza

SYSNO ASEP	0463882
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Kinetic, thermodynamic and structural analysis of tamiphosphor binding to neuraminidase of H1N1 (2009) pandemic influenza
Author(s)	Albinana, C. B. (CZ) Machara, A. (CZ) Řezáčová, Pavlína (UOCHB-X)_{RID, ORCID} Pachl, Petr (UOCHB-X)_{RID, ORCID} Konvalinka, Jan (UOCHB-X)_{RID, ORCID} Kožíšek, Milan (UOCHB-X)_{RID, ORCID}
Source Title	European Journal of Medicinal Chemistry. - : Elsevier - ISSN 0223-5234 Roč. 121, Oct 4 (2016), s. 100-109
Number of pages	10 s.
Language	eng - English
Country	FR - France
Keywords	influenza neuraminidase ; oseltamivir ; tamiphosphor ; isothermal titration calorimetry ; crystal structure ; lattice-translocation defect
Subject RIV	CE - Biochemistry
R&D Projects	GA13-19561S GA ČR - Czech Science Foundation (CSF)
	LO1302 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LO1304 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Institutional support	UOCHB-X - RVO:61388963
UT WOS	000382269700009
EID SCOPUS	84971320756
DOI	10.1016/j.ejmech.2016.05.016
Annotation	Influenza virus causes severe respiratory infections that are responsible for up to half a million deaths worldwide each year. Two inhibitors targeting viral neuraminidase have been approved to date (oseltamivir, zanamivir). However, the rapid development of antiviral drug resistance and the efficient transmission of resistant viruses among humans represent serious threats to public health. The approved influenza neuraminidase inhibitors have (oxa)cyclohexene scaffolds designed to mimic the oxonium transition state during enzymatic cleavage of sialic acid. Their active forms contain a carboxylate that interacts with three arginine residues in the enzyme active site. Recently, the phosphonate group was successfully used as an isostere of the carboxylate in oseltamivir, and the resulting compound, tamiphosphor, was identified as a highly active neuraminidase inhibitor. However, the structure of the complex of this promising inhibitor with neuraminidase has not yet been reported. Here, we analyzed the interaction of a set of oseltamivir and tamiphosphor derivatives with neuraminidase from the A/California/07/2009 (H1N1) influenza virus. We thermodynamically characterized the binding of oseltamivir carboxylate or tamiphosphor to the neuraminidase catalytic domain by protein microcalorimetry, and we determined crystal structure of the catalytic domain in complex with tamiphosphor at 1.8 angstrom resolution. This structural information should aid rational design of the next generation of neuraminidase inhibitors.
Workplace	Institute of Organic Chemistry and Biochemistry
Contact	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Year of Publishing	2017

Number of the records: 1