1ruj
From Proteopedia
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RHINOVIRUS 14 MUTANT WITH SER 1 223 REPLACED BY GLY (S1223G)
Overview
WIN compounds inhibit attachment of human rhinovirus 14 by binding to a, hydrophobic pocket within the capsid and inducing conformational changes, in the canyon floor, the region that binds the cellular receptor. To study, the basis of drug resistance, we isolated and characterized a family of, human rhinovirus 14 mutants resistant to WIN 52035-2. Thermostabilization, data and single-cycle growth curves provided evidence for two classes of, resistant mutants. One class, here called exclusion mutants, showed a, marked decrease in drug-binding affinity and was characterized by, substitution to bulkier amino acid side chains at two sites lining the, hydrophobic pocket. The other class, called compensation mutants, displayed single-amino-acid substitutions in the drug-deformable regions, of the canyon; these mutants were able to attach to cells despite the, presence of bound drug. A delay in the rise period of the growth curves of, compensation mutants indicated a second locus of drug action. WIN 52035-2, was found to inhibit the first step of uncoating, release of VP4. Attempts, to identify this site of drug action by using single-step growth curves, were obscured by abortive elution of a major fraction of cell-attached, virus. The drug had no effect on the rate of this process but did affect, the spectrum of particles produced.
About this Structure
1RUJ is a Protein complex structure of sequences from Human rhinovirus 10. Full crystallographic information is available from OCA.
Reference
WIN 52035-2 inhibits both attachment and eclipse of human rhinovirus 14., Shepard DA, Heinz BA, Rueckert RR, J Virol. 1993 Apr;67(4):2245-54. PMID:8383239
Page seeded by OCA on Wed Nov 21 01:52:49 2007
