Structure, function and mechanism of exocyclic DNA methyltransferases.
DNA MTases (methyltransferases) catalyse the transfer of methyl groups to DNA from AdoMet (S-adenosyl-L-methionine) producing AdoHcy (S-adenosyl-L-homocysteine) and methylated DNA. The C5 and N4 positions of cytosine and N6 position of adenine are the target sites for methylation. All three methylation patterns are found in prokaryotes, whereas cytosine at the C5 position is the only methylation reaction that is known to occur in eukaryotes. In general, MTases are two-domain proteins comprising one large and one small domain with the DNA-binding cleft located at the domain interface. The striking feature of all the structurally characterized DNA MTases is that they share a common core structure referred to as an 'AdoMet-dependent MTase fold'. DNA methylation has been reported to be essential for bacterial virulence, and it has been suggested that DNA adenine MTases (Dams) could be potential targets for both vaccines and antimicrobials. Drugs that block Dam could slow down bacterial growth and therefore drug-design initiatives could result in a whole new generation of antibiotics. The transfer of larger chemical entities in a MTase-catalysed reaction has been reported and this represents an interesting challenge for bio-organic chemists. In general, amino MTases could therefore be used as delivery systems for fluorescent or other reporter groups on to DNA. This is one of the potential applications of DNA MTases towards developing non-radioactive DNA probes and these could have interesting applications in molecular biology. Being nucleotide-sequence-specific, DNA MTases provide excellent model systems for studies on protein-DNA interactions. The focus of this review is on the chemistry, enzymology and structural aspects of exocyclic amino MTases.
Bheemanaik
Shivakumara
S
Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, India.
Reddy
Yeturu V R
YV
Rao
Desirazu N
DN
D000818:Animals; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D019175:DNA Methylation; D007700:Kinetics; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004248:DNA (Cytosine-5-)-Methyltransferases