Functional Dynamics in Chlorella virus DNA Ligase

DNA ligases specifically recognize and seal double stranded nicked DNA by catalyzing the formation of a phospho-diester bond between the 3′OH and 5′ phosphate termini. In physiological conditions these ubiquitous enzymes are essential for DNA replication, repair and recombination, while in tumor cells they can play a critical role in apoptosis resistance.Chlorella virus ligase is a pluripotent ATP-dependent ligase composed by two domains, a N-terminal nucleotidyltransferase domain, hosting the catalytic site, and a C-terminal OB-domain, both of which participate to DNA binding. A number of crystallographic studies have elucidated important structural details of the nick-sealing process. DNA binding, in particular, appears to require a large reorientation of the two domains, as well as relevant structural rearrangements localized mainly in the N-terminal region (1). Indeed this protein appears to be a highly dynamic system whose internal motions are closely linked to both the DNA recognition and to the catalytic process. So far, however, the actual nature of these motions is still largely unknown, not only for Chlorella virus ligase, but also for the entire protein family.We therefore tried to close this gap by undertaking the analysis of the dynamic properties of Chlorella virus liagase by solution NMR spectroscopy.Reference:(1) Nair P.A., Nandakumar J., Smith P., Odell M., Lima C.D., Shuman S. (2008) Nat Struct Mol Biol. 14, 770-8.