Mutagenesis oxidative

Estell, D.A., Graycar, T.P., Wells, J.A. Engineering an enzyme by site-directed mutagenesis to be resistant to chemical oxidation. /. Biol. Chem. 260 6518-6521, 1985. 

Table 9.4 Mutagenesis of CHMOAcineto toward enantiodivergent Baeyer-Villiger oxidations.

Parallel to the modification of the catalytic performance in Baeyer-Villiger oxidations, random mutagenesis was successfully applied to improve the stereoselectivity of CHMOAcineto hi cascs of essentially racemic sulfoxide formation. In addition, enantiodivergent clones with >98% ee for both antipodal products were identified (Table 9.5) [205]. However, improvement in stereoselectivity of mutant enzymes was often accompanied by increased formation of sulfone. This effect can also be utilized to resolve racemic sulfoxides. 

Touati D, M Jacques, B Tardat, L Bouchard, S Despied (1995) Lethal oxidative damage and mutagenesis are generated by iron Afur mutants of Escherichia coli protective role of superoxide dismutase. J Bacterial 111 2305-2314. 

Dedon, P. C. Plastaras, J. P. Rouzer, C. A. Marnett, L. J. Indirect mutagenesis by oxidative DNA damage formation of the pyrimidopurinone adduct of deoxyguanosine by base propenal. Proc. Natl. Acad. Sci. USA 1998, 95, 11113-11116. 

Torres, E. Sandoval, J. V. Rosell, F. I., et al., Site-Directed Mutagenesis Improves the Biocatalytic Activity of Iso-l-Cytochrome-C in Polycyclic-Hydrocarbon Oxidation. Enzyme and Microbial Technology, 1995. 17(11) pp. 1014—1020. 

Not all mutagenesis in IS. coli is dependent on SOS-processing. Mutations may arise quite simply during DNA replication if a base is substituted by or converted to another, incorrect, base. Consider the consequence of oxidative deamination of the base 5-methylcytosine to thymine. Replication followed by daughter strand segregation will result in a G C base pair having been mutated to an A T base pair. Sites containing 5-methylcytosine are hotspots for G C to A T transitions in 12. coli (24). 

A related fibril model for A/ o was proposed based on scanning proline mutagenesis (Williams et al, 2004) and molecular modeling (Guo et al., 2004). This model proposes that residues 15-21, 24-28, and 31-36 form 3 /-strands, with 2 intervening turns formed by residues 22-23 and 29-30 (Fig. 17G). Residues 17 and 34 are placed in close proximity, as double cysteine mutants at these positions form disulfide bonds on oxidation after fibrillization (Shivaprasad and Wetzel, 2004). Since fibrils with this triangular cross section would not be expected to show an H0-A... 

Portugal J, Waring MJ (1987) Interaction of nucleosome core particles with distamycin and echinomycin analysis of the effect of DNA sequences. Nucleic Acids Res 15(3) 885-903 Povirk LF, Goldberg IH (1987) A role of oxidative DNA sugar damage in mutagenesis by neocarzino-statin and bleomycin. Biochimie 69(8) 815-823... 

C. Cherbonnel-Lasserre and M. K. Dosanjh, Suppression of apoptosis by over-expression of Bcl-2 or Bcl-xL promotes survival and mutagenesis after oxidative damage, Biochimie, 1997, 79(9-10), 613. 

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