NS2B/NS3 protease: allosteric effect of mutations associated with the pathogenicity of tick-borne encephalitis virus.
Summary of "NS2B/NS3 protease: allosteric effect of mutations associated with the pathogenicity of tick-borne encephalitis virus."
The sequences of the protease domain of the tick-borne encephalitis (TBE) virus NS3 protein have two amino acid substitutions, 16 R→K and 45 S→F, in the highly pathogenic and poorly pathogenic strains of the virus, respectively. Two models of the NS2B-NS3 protease complex for the highly pathogenic and poorly pathogenic strains of the virus were constructed by homology modeling using the crystal structure of West Nile virus NS2B-NS3 protease as a template; 20 ns molecular dynamic simulations were performed for both models, the trajectories of the dynamic simulations were compared, and the averaged distance between the two models was calculated for each residue. Conformational differences between two models were revealed in the identified pocket. The different conformations of the pocket resulted in different orientations of the NS2B segment located near the catalytic triad. In the model of the highly pathogenic TBE virus the identified pocket had a more open conformation compared to the poorly pathogenic model. We propose that conformational changes in the active protease center, caused by two amino acid substitutions, can influence enzyme functioning and the virulence of the virus.
Affiliation
a Limnological Institute, Siberian Branch of the Russian Academy of Sciences , 3, Ulan-Batorskaya St. , Irkutsk , 664033 , Russian Federation.
Journal Details
This article was published in the following journal.
Name: Journal of biomolecular structure & dynamics
ISSN: 1538-0254
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22730949
- DOI: http://dx.doi.org/10.1080/07391102.2012.689697
Medical and Biotech [MESH] Definitions
Hiv Protease
Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.
Placebo Effect
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
Allosteric Regulation
The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.
Protease Nexins
Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.
Hiv Protease Inhibitors
Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.
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