Počet záznamů: 1
Kinetic, thermodynamic and structural analysis of tamiphosphor binding to neuraminidase of H1N1 (2009) pandemic influenza
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SYSNO ASEP 0463882 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Kinetic, thermodynamic and structural analysis of tamiphosphor binding to neuraminidase of H1N1 (2009) pandemic influenza Tvůrce(i) 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, ORCIDZdroj.dok. European Journal of Medicinal Chemistry. - : Elsevier - ISSN 0223-5234
Roč. 121, Oct 4 (2016), s. 100-109Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. FR - Francie Klíč. slova influenza neuraminidase ; oseltamivir ; tamiphosphor ; isothermal titration calorimetry ; crystal structure ; lattice-translocation defect Vědní obor RIV CE - Biochemie CEP GA13-19561S GA ČR - Grantová agentura ČR LO1302 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LO1304 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000382269700009 EID SCOPUS 84971320756 DOI 10.1016/j.ejmech.2016.05.016 Anotace 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2017
Počet záznamů: 1