| Summary: | Ribonucleotide reductase is the only enzyme that is involved in de novo synthesis of DNA.
Herpes Virus Ribonucleotide reductase consists of two subunits R1 and R2, The activation of
this enzyme is controlled by the binding of the allosteric sites on R1 and the radical generation in
R2. Crystallographic studies of the R2 subunits from various organisms have revealed a
conserved divalent metal site, but the nature of the metals bound seems to differ, especially in
human pathogens like clamydia. Until now, no structures have been reported in the literature of
the human herpes virus R2s and no information exists on its metal preference for the generation
of the radical. In this thesis, the expression and purification of alpha and gamma subtype herpes
virus protein were performed. For investigation of metal binding capacity, herpes viral R2
proteins were recombinantly expressed and purified and a method for extraction of any present
metals and insertion of the new metals was developed. Initial crystal screening of R2 proteins
with different divalent metal were set up. One of initial crystal of ORF18-R2 containing MgCl 2
was diffracted to 2.8 Å. A structure of a human herpes virus R2 with its preferred metal ion
bound could potentially provide more information for the development of more specific antiviral
drugs.
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