Cover: DNA base flipping is a mechanism used by a host of enzymes whose functions rely on intimate contact between a DNA base and the enzyme’s active site. The illustration shows the crystal structure of one such enzyme, M.HhaI, bound to a synthetic DNA duplex in which the fluorescent adenine analogue, 2-aminopurine (AP), is at the target site. The AP base, shown in yellow, is flipped out of the DNA duplex into the catalytic cleft of the enzyme. In the plot at the top right, the fluorescence decay curve of the flipped-out AP in this crystalline complex is shown in yellow. The fluorescence decay of unflipped AP, shown in red, was recorded for a crystalline M.HhaI–DNA complex with AP located away from the target site. The same clear response of the AP fluorescence decay to base flipping is observed when M.HhaI complexes with DNA in solution. For further information see the paper by Neely et al. in this issue [Nucleic Acids Res. (2005) 33, 6953–6960].
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