1qju: Difference between revisions

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.

1QJU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_rhinovirus_14 Human rhinovirus 14] with ZN, MYR and W01 as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Sites: MYR, POC, RNA and ZN. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QJU OCA].  

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 14:02:52 2007''