1QJX

HUMAN RHINOVIRUS 16 COAT PROTEIN IN COMPLEX WITH ANTIVIRAL COMPOUND WIN68934

Summary for 1QJX

• Entry DOI: 10.2210/pdb1qjx/pdb
• Related: 1AYM 1AYN 1C8M 1D3E 1NCR 1ND2 1ND3 1QJU 1QJX 1QJY 1QJZ 1TP7 1XR7
• Descriptor: PROTEIN VP1, PROTEIN VP2, PROTEIN VP3, ... (8 entities in total)
• Functional Keywords: virus, nucleotidyltransferase, rhinovirus coat protein, rna-binding, transferase, lipoprotein, win compound, phosphoprotein, thiol protease, capsid protein, drug, virion, membrane, helicase, protease, nucleotide-binding, human rhinovirus 16, rna replication, antiviral compound, covalent protein-rna linkage, myristate, hydrolase, cytoplasm, atp-binding, cytoplasmic vesicle, host-virus interaction, rna-directed rna polymerase
• Biological source: HUMAN RHINOVIRUS 16 (HRV-16); More
• Total number of polymer chains: 4
• Total formula weight: 95801.34

Authors

Hadfield, A.T.,Diana, G.D.,Rossmann, M.G. (deposition date: 1999-07-06, release date: 1999-07-20, Last modification date: 2024-11-13)

Primary citation

Hadfield, A.T.,Minor, I.,Diana, G.D.,Rossmann, M.G.
Analysis of Three Structurally Related Antiviral Compounds in Complex with Human Rhinovirus 16
Proc.Natl.Acad.Sci.USA, 96:14730-, 1999

PubMed Abstract: Rhinoviruses are a frequent cause of the common cold. A series of antirhinoviral compounds have been developed that bind into a hydrophobic pocket in the viral capsid, stabilizing the capsid and interfering with cell attachment. The structures of a variety of such compounds, complexed with rhinovirus serotypes 14, 16, 1A, and 3, previously have been examined. Three chemically similar compounds, closely related to a drug that is undergoing phase III clinical trials, were chosen to determine the structural impact of the heteroatoms in one of the three rings. The compounds were found to have binding modes that depend on their electronic distribution. In the compound with the lowest efficacy, the terminal ring is displaced by 1 A and rotated by 180 degrees relative to the structure of the other two. The greater polarity of the terminal ring in one of the three compounds leads to a small displacement of its position relative to the other compounds in the hydrophobic end of the antiviral compound binding pocket to a site where it makes fewer interactions. Its lower efficacy is likely to be the result of the reduced number of interactions. A region of conserved residues has been identified near the entrance to the binding pocket where there is a corresponding conservation of the mode of binding of these compounds to different serotypes. Thus, variations in residues lining the more hydrophobic end of the pocket are primarily responsible for the differences in drug efficacies.

PubMed: 10611281
DOI: 10.1073/PNAS.96.26.14730

Experimental method

X-RAY DIFFRACTION (2.8 Å)