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Instruments / Technical Area	Publication Details	Published	Actions
I04-Macromolecular Crystallography	Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization Jorge Donderis , Janine Bowring , Elisa Maiques , J. Rafael Ciges-Tomas , Christian Alite , Iltyar Mehmedov , María Angeles Tormo-Mas , José R. Penadés , Alberto Marina Plos Pathogens 13 DOI: 10.1371/journal.ppat.1006581 Diamond Proposal Number(s): [14739] Open Access Show Abstract ▼ Abstract: The dUTPase (Dut) enzymes, encoded by almost all free-living organisms and some viruses, prevent the misincorporation of uracil into DNA. We previously proposed that trimeric Duts are regulatory proteins involved in different cellular processes; including the phage-mediated transfer of the Staphylococcus aureus pathogenicity island SaPIbov1. Recently, it has been shown that the structurally unrelated dimeric Dut encoded by phage ϕNM1 is similarly able to mobilize SaPIbov1, suggesting dimeric Duts could also be regulatory proteins. How this is accomplished remains unsolved. Here, using in vivo, biochemical and structural approaches, we provide insights into the signaling mechanism used by the dimeric Duts to induce the SaPIbov1 cycle. As reported for the trimeric Duts, dimeric Duts contain an extremely variable region, here named domain VI, which is involved in the regulatory capacity of these enzymes. Remarkably, our results also show that the dimeric Dut signaling mechanism is modulated by dUTP, as with the trimeric Duts. Overall, our results demonstrate that although unrelated both in sequence and structure, dimeric and trimeric Duts control SaPI transfer by analogous mechanisms, representing a fascinating example of convergent evolution. This conserved mode of action highlights the biological significance of Duts as regulatory molecules.	Sep 2017

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I04-Macromolecular Crystallography

Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization

Jorge Donderis , Janine Bowring , Elisa Maiques , J. Rafael Ciges-Tomas , Christian Alite , Iltyar Mehmedov , María Angeles Tormo-Mas , José R. Penadés , Alberto Marina

Plos Pathogens 13

DOI: 10.1371/journal.ppat.1006581

Diamond Proposal Number(s): [14739]