Molecular Mimetism As An Enzyme Inhibitor
These strategies could be considered intelligent, calculated actions, since viruses can either take over some of the cell’s components and use them for their own benefit or deactivate particular functions of the cell in order to allow for a more effective and trouble free infection process.
This very interesting subject has been the focus of the investigations of the “Centro de Biología Molecular Severo Ochoa” (CBMSO; UAM-CSIC) working together with the “Centro de Investigaciones Biológicas (CIB; CSIC)”.
The outcome of their research on viral strategies that affect cellular functions has recently been published.
For several years, Professor Margarita Salas from the CBMSO has dedicated part of her research efforts to the study of the replication mechanism of virus 29, which infects the Bacillus subtilis, harmless bacteria commonly found in the soil. Her work has contributed towards a better understanding of the interactions between the viruses and their target cells at a molecular level. In an article published last year in the Journal of Biological Chemistry (Vol. 281: 7068-7074; 2006), Professor Salas and her team described an important discovery: the protein p56 of virus 29 inhibits the activity of the cellular protein uracil-DNA-glycosylase (UDG). It is known that this enzyme, present in all living organisms, is involved in the DNA repair processes and hence, it avoids mutations in the cellular genome.
In order to carry out its function, the UDG enzyme first identifies the damaged DNA by locating uracil residues and then attaches itself to the DNA to repair it. Recently, Professor Salas team, in collaboration with the research group managed by Professor Manuel Espinosa from the CIB, have published their new discoveries in Nucleic Acids Research (Vol. 35: 5393-5401; 2007), recounting how the viral protein p56 manages to inhibit the activity of the UDG enzyme. Their experiments show that the protein p56 conceals the part of the UDG enzyme that interacts with the damaged DNA so that there is no possibility of attachment.
The protein p56 might accomplish this by imitating the structural characteristics of DNA in order to mislead the UDG enzyme. If the theory is corroborated, this would be another case of molecular mimesis as an enzyme inhibitor technique. The future work by Professor Salas and her team will be dedicated to substantiating this hypothesis.
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