| Literature References | 1. CHENG, X.
DNA modification by methyltransferases.
CURR.OPIN.STRUCT.BIOL. 5 4-10 (1995).
2. KUMAR, S., CHENG, X., KLIMASAUSKAS, S., MI., S., POSFAI, J., ROBERTS,
R.J. AND WILSON, G.G.
The DNA (cytosine-5) methyltransferases.
NUCLEIC ACIDS RES. 22 1-10 (1994).
3. CHENG, X., KUMAR, S., POSFAI, J., PFLUGRATH, J.W. AND ROBERTS, R.J.
Crystal structure of the HhaI methyltransferase complexed with
S-adenosyl-L-methionine.
CELL 74 299-307 (1993).
4. POSFAI, J., BHAGWAT, A.S. AND ROBERTS, R.J.
Sequence motifs for cytosine methyltransferases.
GENE 74 261-265 (1988).
5. KLIMASAUSKAS, S., KUMAR, S., ROBERTS, R.J. AND CHENG, X.
HhaI methyltransferase flips its target base out of the DNA helix.
CELL 76 357-369 (1994).
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| Documentation | DNA (C5-cytosine) methyltransferases catalyse the methylation of the ring
carbon of cytosine in specific DNA sequences to produce C5-methylcytosine
[1]. In mammalian cells, cytosine-specific methyltransferases methylate
certain CpG sequences, which are believed to modulate gene expression and
cell differentiation. In bacteria, these enzymes are a component of
restriction-modification systems and serve as valuable tools for the
manipulation of DNA [1,2]. The structure of HhaI methyltransferase (M.HhaI)
has been resolved to 2.5 A [3]: the molecule folds into 2 domains - a
larger catalytic domain containing catalytic and cofactor binding sites,
and a smaller DNA recognition domain.
C5METTRFRASE is a 3-element fingerprint that provides a signature for the
cytosine-specific methyltransferases. The fingerprint was derived from an
initial alignment of 11 sequences: the motifs were drawn from some of the
conserved regions identified by Posfai et al. [4] - motif 1 contains the
pattern FAGxGG, which forms part of the cofactor S-adenosyl-L-methionine
(SAM) binding site [3]; motifs 2 and 3 contain conserved Glu and Arg
residues, respectively, corresponding to Glu-119 and Arg-165 in HhaI, which
form a salt bridge in the binary complex of HhaI with SAM [3] (cf. PROSITE
patterns C5_MTASE_1 and C5_MTASE_2). Upon DNA binding, the ion pair is
disrupted and both side chains interact with polar groups of the target
cytosine [5]. Two iterations on OWL10.1 were required to reach convergence,
at which point a true set comprising 26 sequences was identified.
An update on SPTR37_9f identified a true set of 100 sequences, and 14
partial matches.
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