1RMU

THREE-DIMENSIONAL STRUCTURES OF DRUG-RESISTANT MUTANTS OF HUMAN RHINOVIRUS 14

Summary for 1RMU

• Entry DOI: 10.2210/pdb1rmu/pdb
• Descriptor: HUMAN RHINOVIRUS 14 COAT PROTEIN (SUBUNIT VP1), HUMAN RHINOVIRUS 14 COAT PROTEIN (SUBUNIT VP2), HUMAN RHINOVIRUS 14 COAT PROTEIN (SUBUNIT VP3), ... (6 entities in total)
• Functional Keywords: rhinovirus coat protein, icosahedral virus, virus
• Biological source: Human rhinovirus 14; More
• Cellular location: Protein VP2: Virion. Protein VP3: Virion. Protein VP1: Virion. Protein 2B: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 2C: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 3A: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential). Protein 3B: Virion (Potential). Picornain 3C: Host cytoplasm (Potential). RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (Potential): P03303 P03303 P03303 P03303
• Total number of polymer chains: 4
• Total formula weight: 94664.70

Authors

Badger, J.,Krishnaswamy, S.,Kremer, M.J.,Oliveira, M.A.,Rossmann, M.G.,Heinz, B.A.,Rueckert, R.R.,Dutko, F.J.,Mckinlay, M.A. (deposition date: 1988-10-03, release date: 1990-01-15, Last modification date: 2024-05-22)

Primary citation

Badger, J.,Krishnaswamy, S.,Kremer, M.J.,Oliveira, M.A.,Rossmann, M.G.,Heinz, B.A.,Rueckert, R.R.,Dutko, F.J.,McKinlay, M.A.
Three-dimensional structures of drug-resistant mutants of human rhinovirus 14.
J.Mol.Biol., 207:163-174, 1989

PubMed Abstract: Mutants of human rhinovirus 14 were isolated and characterized by searching for resistance to compounds that inhibit viral uncoating. The portions of the RNA that code for amino acids that surround the antiviral compound binding site were sequenced. X-ray analysis of two of these mutants, 1188 Val----Leu and 1199 Cys----Tyr, shows that these were single-site substitutions which would sterically hinder drug binding. Differences in the resistance of mutant viruses to various antiviral compounds may be rationalized in terms of the three-dimensional structures of these mutants. Predictions of the structures of mutant rhinovirus 14 with the substitutions 1188 Val----Leu, 1199 Cys----Tyr and 1199 Cys----Trp in VP1 were made using a molecular dynamics technique. The predicted structure of the 1199 Cys----Tyr mutant was consistent with the electron density map, while the 1188 Val----Leu prediction was not. Large (up to 1.4 A) conformational differences between native rhinovirus 14 and the 1199 Cys----Tyr mutant occurred in main-chain atoms near the mutation site. These changes, as well as the orientation of the 1199 tyrosine side-chain, were correctly predicted by the molecular dynamics calculation. The structure of the predicted 1199 Cys----Trp mutation is consistent with the drug-resistant properties of this virus.

PubMed: 2544734
DOI: 10.1016/0022-2836(89)90447-6

Experimental method

X-RAY DIFFRACTION (3 Å)