Structural Basis for Specific Recognition of Substrates by Sapovirus Protease
Open Access
- 1 January 2012
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Microbiology
- Vol. 3, 31331
- https://doi.org/10.3389/fmicb.2012.00312
Abstract
Sapovirus (SaV) protease catalyzes cleavage of the peptide bonds at six sites of a viral polyprotein for the viral replication and maturation. However, the mechanisms by which the protease recognizes the distinct sequences of the six cleavage sites remain poorly understood. Here we examined this issue by computational and experimental approaches. A structural modeling and docking study disclosed two small clefts on the SaV protease cavity that allow the stable and functional binding of substrates to the catalytic cavity via aromatic stacking and electrostatic interactions. An information entropy study and a site-directed mutagenesis study consistently suggested variability of the two clefts under functional constraints. Using this information, we identified three chemical compounds that had structural and spatial features resembling those of the substrate amino acid residues bound to the two clefts and that exhibited an inhibitory effect on SaV protease in vitro. These results suggest that the two clefts provide structural base points to realize the functional binding of various substrates.This publication has 46 references indexed in Scilit:
- Comparison of the replication properties of murine and human calicivirus RNA-dependent RNA polymerasesVirus Genes, 2010
- Estimating child mortality due to diarrhoea in developing countriesBulletin of the World Health Organization, 2008
- ASEDock-Docking Based on Alpha Spheres and Excluded VolumesJournal of Chemical Information and Modeling, 2008
- Human sapoviruses: genetic diversity, recombination, and classificationReviews in Medical Virology, 2007
- Structural and Functional Characterization of Sapovirus RNA-Dependent RNA PolymeraseJournal of Virology, 2007
- In Vitro Proteolytic Processing of the MD145 Norovirus ORF1 Nonstructural Polyprotein Yields Stable Precursors and Products Similar to Those Detected in Calicivirus-Infected CellsJournal of Virology, 2003
- Protein Structure Prediction and Structural GenomicsScience, 2001
- Sapporo Virus: History and Recent FindingsThe Journal of Infectious Diseases, 2000
- Crystal Structure of an Inhibitor Complex of the 3C Proteinase from Hepatitis A Virus (HAV) and Implications for the Polyprotein Processing in HAVVirology, 1999
- An outbreak of gastroenteritis associated with calicivirus in an infant homeJournal of Medical Virology, 1979