Literature DB >> 7516598

Neutron diffraction reveals the site of amantadine blockade in the influenza A M2 ion channel.

K C Duff1, P J Gilchrist, A M Saxena, J P Bradshaw.   

Abstract

The influenza A M2 protein forms proton channels which are blocked by the anti-influenza drug amantadine. Using the technique of neutron diffraction with both deuterium-labeled amantadine and influenza A M2 peptides, this study has directly located the position of interaction between the drug and the transmembrane domain of M2. Amantadine is found 0.5 nm from the center of the bilayer in an area between Val 27 and Ser 31, a location consistent with the formation of a steric block within the ion channel. Similar experiments with amantadine and an amantadine-resistant mutant peptide showed no such interaction.

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Year:  1994        PMID: 7516598     DOI: 10.1006/viro.1994.1345

Source DB:  PubMed          Journal:  Virology        ISSN: 0042-6822            Impact factor:   3.616


  33 in total

1.  pH-dependent tetramerization and amantadine binding of the transmembrane helix of M2 from the influenza A virus.

Authors:  D Salom; B R Hill; J D Lear; W F DeGrado
Journal:  Biochemistry       Date:  2000-11-21       Impact factor: 3.162

2.  Structure of the transmembrane region of the M2 protein H(+) channel.

Authors:  J Wang; S Kim; F Kovacs; T A Cross
Journal:  Protein Sci       Date:  2001-11       Impact factor: 6.725

3.  Contribution of energy values to the analysis of global searching molecular dynamics simulations of transmembrane helical bundles.

Authors:  Jaume Torres; John A G Briggs; Isaiah T Arkin
Journal:  Biophys J       Date:  2002-06       Impact factor: 4.033

4.  Effect of cytoplasmic tail truncations on the activity of the M(2) ion channel of influenza A virus.

Authors:  K Tobler; M L Kelly; L H Pinto; R A Lamb
Journal:  J Virol       Date:  1999-12       Impact factor: 5.103

5.  Influence of an additional amino group on the potency of aminoadamantanes against influenza virus A. II - Synthesis of spiropiperazines and in vitro activity against influenza A H3N2 virus.

Authors:  Christos Fytas; Antonios Kolocouris; George Fytas; Grigoris Zoidis; Charalampos Valmas; Christopher F Basler
Journal:  Bioorg Chem       Date:  2010-09-21       Impact factor: 5.275

6.  Assembly of the m2 tetramer is strongly modulated by lipid chain length.

Authors:  Sandra Schick; Lirong Chen; Edwin Li; Janice Lin; Ingo Köper; Kalina Hristova
Journal:  Biophys J       Date:  2010-09-22       Impact factor: 4.033

Review 7.  Flu channel drug resistance: a tale of two sites.

Authors:  Rafal M Pielak; James J Chou
Journal:  Protein Cell       Date:  2010-02-23       Impact factor: 14.870

8.  Distribution and dynamics of adamantanes in a lipid bilayer.

Authors:  Chee Foong Chew; Andrew Guy; Philip C Biggin
Journal:  Biophys J       Date:  2008-10-03       Impact factor: 4.033

9.  A secondary gate as a mechanism for inhibition of the M2 proton channel by amantadine.

Authors:  Myunggi Yi; Timothy A Cross; Huan-Xiang Zhou
Journal:  J Phys Chem B       Date:  2008-05-14       Impact factor: 2.991

10.  Design and pharmacological characterization of inhibitors of amantadine-resistant mutants of the M2 ion channel of influenza A virus.

Authors:  Victoria Balannik; Jun Wang; Yuki Ohigashi; Xianghong Jing; Emma Magavern; Robert A Lamb; William F Degrado; Lawrence H Pinto
Journal:  Biochemistry       Date:  2009-12-22       Impact factor: 3.162

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