Increased Dissociation of Adamantanamines in Influenza A M2 S31N with Partial Block by Rimantadine.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
03 11 2020
03 11 2020
Historique:
received:
20
04
2020
revised:
06
08
2020
accepted:
15
09
2020
pubmed:
21
10
2020
medline:
15
5
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
The ubiquitous mutation from serine (WT) to asparagine at residue 31 (S31N) in the influenza A M2 channel renders it insensitive to amantadine (AMT) and rimantadine (RMT) block, but it is unknown whether the inhibition results from weak binding or incomplete block. Two-electrode voltage clamp (TEVC) of transfected Xenopus oocytes revealed that the M2 S31N channel is essentially fully blocked by AMT at 10 mM, demonstrating that, albeit weak, AMT binding in a channel results in complete block of its proton current. In contrast, RMT achieves only a modest degree of block in the M2 S31N channel at 1 mM, with very little increase in block at 10 mM, indicating that the RMT binding site in the channel saturates with only modest block. From exponential curve fits to families of proton current wash-in and wash-out traces, the association rate constant (k
Identifiants
pubmed: 33080223
pii: S0006-3495(20)30726-8
doi: 10.1016/j.bpj.2020.09.015
pmc: PMC7677129
pii:
doi:
Substances chimiques
Antiviral Agents
0
Viral Matrix Proteins
0
Rimantadine
0T2EF4JQTU
Amantadine
BF4C9Z1J53
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1811-1820Informations de copyright
Copyright © 2020 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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