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This example invitations the design of C-two-substituted analogs of adenosine nucleotides and NAD+ as selective inhibitors of LigA. In fact, it had been documented just lately that 2-methylthio-ATP is often a potent inhibitor with the adenylylation response of E. coli
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Ideally, one would wish to engineer a DNA ligase mutant able to binding an adenosine analog that is Usually excluded from the active site of the wild-kind ligase. Changing the wild-form ligase With all the analog-delicate ligase in an organism that has many ligase isozymes could permit selective and swift inhibition of strand sealing, without depleting the ligase protein and without the need of impacting the numerous other proteins that connect with DNA ligases in mammalian cells (2, 3).
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