Recombinant Variola virus Ribonucleoside-diphosphate reductase large subunit (I4L, K4L, ORF3L), partial
Description
Recombinant Expression and Applications
Partial recombinant forms of this protein are produced to study:
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Enzyme kinetics: Substrate binding and catalytic efficiency compared to full-length or host RNRs.
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Virus-host interactions: Formation of hybrid RNR complexes with human R1 or R2 subunits .
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Drug targeting: Screening for inhibitors that disrupt dNTP synthesis in poxvirus-infected cells.
Table 1: Key Research Findings on Variola RNR Large Subunit
Evolutionary and Pathogenic Significance
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Conservation: Orthopoxvirus R1 subunits share >70% sequence identity with mammalian homologs, enabling cross-species interactions .
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Pathogenesis: Despite encoding both R1 and R2 subunits, Variola R2 is more critical for virulence, as observed in vaccinia virus models .
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Therapeutic potential: RNR-deficient poxviruses show attenuated growth in normal cells but replicate in cancer cells with elevated RNR activity, suggesting oncolytic applications .
