H274Y's effect on oseltamivir resistance : what happens before the drug enters the binding site

Yusuf, Muhammad; Mohamed, Nornisah; Mohamad, Suriyati; Janežič, Dušanka; Damodaran, K. V.; Wahab, Habibah A.

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Naslov:	H274Y's effect on oseltamivir resistance : what happens before the drug enters the binding site
Avtorji:	ID Yusuf, Muhammad (Avtor) ID Mohamed, Nornisah (Avtor) ID Mohamad, Suriyati (Avtor) ID Janežič, Dušanka (Avtor) ID Damodaran, K. V. (Avtor) ID Wahab, Habibah A. (Avtor)
Datoteke:	http://pubs.acs.org/doi/ipdf/10.1021/acs.jcim.5b00331
Jezik:	Angleški jezik
Vrsta gradiva:	Delo ni kategorizirano
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	IAM - Inštitut Andrej Marušič
Opis:	Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H274Y focused only on the drug-bound system, so the direct effects of the mutation on NA itself prior to drug binding still remain unclear. Therefore, molecular dynamics simulations of NA in apo form, followed by principal component analysis and interaction energy calculations, were performed to investigate the structural changes of the NA binding site as a result of the H274Y mutation. It was observed that the disruption of the NA binding site due to the H274Y mutation was initiated by the repulsive effect of Y274 on the 250-loop, which in turn altered the hydrogen-bonding network around residue 274. The rotated W295 side chain caused the upward movement of the 340-loop. Consequently, sliding box docking results suggested that the binding pathway of OTV was compromised because of the disruption of this binding site. This study also highlighted the importance of the functional group at C6 of the sialic acid mimicry. It is hoped that these results will improve the understanding of OTV resistance and shed some light on the design of a novel anti-influenza drug.
Ključne besede:	influenza, neuraminidase, H274Y, oseltamivir, molecular dynamics
Leto izida:	2016
Št. strani:	str. 82-100
Številčenje:	Vol. 56, iss. 1
PID:	20.500.12556/RUP-8400
ISSN:	1549-9596
UDK:	544.1
DOI:	10.1021/acs.jcim.5b00331
COBISS.SI-ID:	1538117060
Datum objave v RUP:	08.08.2016
Število ogledov:	3597
Število prenosov:	148
Metapodatki:
:	YUSUF, Muhammad, MOHAMED, Nornisah, MOHAMAD, Suriyati, JANEŽIČ, Dušanka, DAMODARAN, K. V. in WAHAB, Habibah A., 2016, H274Y’s effect on oseltamivir resistance : what happens before the drug enters the binding site. [na spletu]. 2016. Vol. 56, no. 1, p. 82–100. [Dostopano 13 april 2025]. DOI 10.1021/acs.jcim.5b00331. Pridobljeno s: http://pubs.acs.org/doi/ipdf/10.1021/acs.jcim.5b00331 Kopiraj citat

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