Ligand-induced conformational changes in poliovirus-antiviral drug complexes.Hiremath, C.N., Filman, D.J., Grant, R.A., Hogle, J.M.
(1997) Acta Crystallogr.,Sect.D 53: 558-570
- PubMed: 15299887
- DOI: 10.1107/S0907444997000954
- Primary Citation of Related Structures:
- PubMed Abstract:
- Structural Factors that Control Conformational Transitions and Serotype Specificity in Type 3 Poliovirus
Filman, D.J.,Syed, R.,Chow, M.,Macadam, A.J.,Minor, P.D.,Hogle, J.M.
(1989) Embo J. 8: 1567
- The Nucleotide Sequence of Poliovirus Type 3 Leon 12 A1B: Comparison with Poliovirus Type 1
Stanway, G.,Cann, A.J.,Hauptmann, R.,Hughes, P.,Clarke, L.D.,Mountford, R.C.,Minor, P.D.,Schild, G.C.,Almond, J.W.
(1983) Nucleic Acids Res. 11: 5629
- Role of Conformational Transitions in Poliovirus Assembly and Cell Entry
Hogle, J.M.,Syed, R.,Fricks, C.E.,Icenogle, J.P.,Flore, O.,Filman, D.J.
(1990) New Aspects of Positive-Strand RNA Viruses --: 199
- Myristylation of Picornavirus Capsid Protein Vp4 and its Structural Significance
Chow, M.,Newman, J.F.,Filman, D.,Hogle, J.M.,Rowlands, D.J.,Brown, F.
(1987) Nature 327: 482
- Structures of Poliovirus Complexes with Anti-Viral Drugs: Implications for Viral Stability and Drug Design
Grant, R.A.,Hiremath, C.N.,Filman, D.J.,Syed, R.,Andries, K.,Hogle, J.M.
(1994) Curr.Biol. 4: 784
- Three-Dimensional Structure of Poliovirus at 2.9 A Resolution
Hogle, J.M.,Chow, M.,Filman, D.J.
(1985) Science 229: 1358
- Binding of the Antiviral Drug Win51711 to the Sabin Strain of Type 3 Poliovirus: Structural Comparison with Drug Binding in Rhinovirus 14
Hiremath, C.N.,Grant, R.A.,Filman, D.J.,Hogle, J.M.
(1995) Acta Crystallogr.,Sect.D 51: 473
Crystal structures of the Mahoney strain of type 1 poliovirus complexed with the antiviral compounds R80633 and R77975 were determined at 2.9 A resolution. These compounds block infection by preventing conformational changes required for viral uncoat ...
Crystal structures of the Mahoney strain of type 1 poliovirus complexed with the antiviral compounds R80633 and R77975 were determined at 2.9 A resolution. These compounds block infection by preventing conformational changes required for viral uncoating. In various drug-poliovirus complexes reported earlier, no significant conformational changes were found in the structures of the capsid proteins. In the structures reported here, the strain of virus is relatively insensitive to these antivirals. Correspondingly, significant conformational changes are necessary to accommodate the drug. These conformational changes affect both the immediate vicinity of the drug binding site, and more distant loops located near the fivefold axis. In addition, small but concerted shifts of the centers of mass of the major capsid proteins consistently have been detected whose magnitudes are correlated inversely with the effectiveness of the drugs. Collectively, the drug complexes appear to sample the conformational repertoire of poliovirus near equilibrium, and thus provide a possible model for the earliest stages of viral uncoating during infection.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.