Base flipping

Overall, it can be envisioned that the Py-G group 47 represents an important label for the time-resolved studies of DNA dynamics and stacking interaction [123] and could be applied especially for assays in which conformational changes or base-flipping processes are essential in observation, such as in the investigation of DNA-protein complexes with DNA repair proteins. 

Neither structure provides a direct view on the catalytic mechanism of these enzymes. However, prior biochemical and structural studies on bacterial MTases in complex with DNA revealed a mechanism involving base-flipping followed by a nudeophilic attack of a conserved cysteine on carbon C6 of the cytosine to be... 

Fig. 4.6.4. Assay for investigation of protein-modulated CT (top). The effect of the protein is apparent from the relative amounts of oxidative G damage (Gox) at the proximal and distal GG pairs. For example, base-flipping of the target C in the binding sequence of M.Hhat decreases the efficiency of HT through the DNA-protein complex. In wild-type M.Hhat the...

Roberts RJ, Cheng X. Base flipping. Annu. Rev. Biochem. 1998 67 181-198. 

Lariviere L, Morera S. A base-flipping mechanism for the T4 phage 3-glucosyltransferase and identification of a transition-state analog. J. Mol. Biol. 2002 324 483-490. 

Lariviere L, Sommer N, Morera S. Structural evidence of a passive base-flipping mechanism for ACT, an unusual GT-B glycosyltransferase. J. Mol. Biol. 2005 352 139-150. 

An interesting study using the base flipping enzyme Methyl-transferase Hhal (M.Hhal) showed that disruption of the it-stack by protein binding with insertion of a nonaromatic amino acid... 

Cheng X, Roberts RJ. AdoMet-dependent methylation, DNA methyltransferases and base flipping. Nucleic Acids Res. 2001 29 3784-3795. 

Figure 3 A stereoview close-up of the acyltransfer site of the 30 S ribosome revealing the based flipping event that is experimented by A1492 and A1493 during a molecular dynamics simulation (see Reference 70). RNA backbone is shown in purple tube representation whereas bases are shown in capped sticks rendering.

Bischerour J, Chalmers R. Base-flipping dynamics in a DNA hairpin processing reaction. Nucleic Acids Res. 2007 35 2584-2595. 

The pseudorotationally constrained abasic site (55), based on bicyclo[3.1.0] hexane, has been incorporated into the methyltransferase M.Hhal recognition sequence to probe the mechanism of base flipping.Binding affinity increases when the abasic sugar is constrained to the north configuration, and is related to the ability of the abasic sugar to flip out of the DNA duplex. 

E.E. Kryachko, J.R. Sabin, Quantum Chemical Study of the Hydrogen-Bonded Patterns in the AT Base Pair of DNA The Origins of Tautomeric Mispairs, Base Flipping, and Watson-Crick Hoogsteen Conversion, Int. J. Quantum Chem. 91 (2003) 695. 

Bernards, A. S., Miller, J. K., Bao, K. K., and Wong, 1. (2002). Flipping duplex DNA inside out A double base-flipping reaction mechanism by Escherichia coli MutY adenine glycosylase./. Biol. Chem. 277, 20960-20964. 

Jiang, Y. L., and Stivers, J. T. (2002). Mutational analysis of the base-flipping mechanism of uracil DNA glycosylase. Biochemistry 41,11236-11247. 

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