| Literature References | 1. CHENG, X.
Structure and function of DNA methyltransferases.
ANNU.REV.BIOPHYS.BIOMOL.STRUCT. 24 293-318 (1995).
2. LABAHN, J., GRANZIN, J., SCHLUCKEBIER, G., ROBINSON, D.P., JACK, W.E.,
SCHILDKRAUT, I. AND SAENGER, W.
Three-dimensional structure of the adenine-specific DNA methyltransferase
M.TaqI in complex with the cofactor S-adenosylmethionine.
PROC.NATL.ACAD.SCI.U.S.A. 91 10957-10961 (1994).
3. TIMINSKAS, A., BUTKUS, V. AND JANULAITIS, A.
Sequence motifs characteristic for DNA [cytosine-N4] and DNA [adenine-N6]
methyltransferases. Classification of all DNA methyltransferases.
GENE 157 3-11 (1995).
4. WILLCOCK, D.F., DRYDEN, D.T. AND MURRAY, N.E.
A mutational analysis of the two motifs common to adenine
methyltransferases.
EMBO J. 13 3902-3908 (1994).
|
| Documentation | In prokaryotes, the major role of DNA methylation is to protect host
DNA against degradation by restriction enzymes. There are 2 major classes
of DNA methyltransferase that differ in the nature of the modifications
they effect [1]. The members of one class (C-MTases) methylate a ring
carbon and form C5-methylcytosine (see PRINTS signature C5METTRFRASE).
Members of the second class (N-MTases) methylate exocyclic nitrogens and
form either N4-methylcytosine (N4-MTases) or N6-methyladenine (N6-MTases).
Both classes of MTase utilise the cofactor S-adenosyl-L-methionine (SAM)
as the methyl donor and are active as monomeric enzymes [1].
The structure of N6-MTase TaqI (M.TaqI) has been resolved to 2.4A [2].
The molecule folds into 2 domains: an N-terminal catalytic domain, which
contains the catalytic and cofactor binding sites, and comprises a central
9-stranded beta-sheet, surrounded by 5 helices; and a C-terminal DNA
recognition domain, which is formed by 4 small beta-sheets and 8 alpha-
helices. The N- and C-terminal domains form a cleft that accommodates the
DNA substrate.
A classification of N-MTases has been proposed, based on conserved motif
(CM) arrangements [3]. According to this classification, N6-MTases that
have a DPPY motif (CM II) occuring before the FxGxG motif (CM I) are
designated D21 class N6-adenine MTases.
D21N6MTFRASE is a 4-element fingerprint that provides a signature for the
D21 class N6-adenine MTases. The fingerprint was derived from an initial
alignment of 13 sequences. The motifs were drawn from the conserved
regions used by Timinskas et al. [3] in their DNA MTase classification:
the motifs correspond to CM II, III, Is and I, respectively - motif 1,
which contains the N-MTase-specific tetrapeptide DPPY (cf. PROSITE pattern
N6_MTASE), is important for methylation; and motif 4, which contains the
FxGxG pattern, forms part of the cofactor (SAM) binding site [4]. Three
iterations on OWL27.1 were required to reach convergence, at which point a
true set comprising 22 sequences was identified. Several partial matches
were also found: S53866 is a phage HP1 cytosine MTase (M.PhiHII) that fails
to match motif 3; MTC9_CITFR (M.Cfr9I), MTC1_CITFR (M.CfrBI) and MTX1_XANCC
(XcyI) fail to match motif 1 and belong to the S21 class N4-cytosine MTases;
MTB2_BACAM (M.BamHII) and MTP2_PROVU (M.PvuII), which match motifs 3 and 4,
and MTSM_SERMA (M.SmaI), which match motifs 2 and 4, also belong to the S21
class N4-cytosine MTases; MTB3_BACAR, BAMBAN111 (M.BanIII), MTB1_BACST
(M.BseCI), MTTA_THEAQ and TATAQI (M.TaqI), which match motifs 1 and 2, are
N12 class N6-adenine MTases, with CM I occuring before the CM II.
An update on SPTR37_9f identified a true set of 54 sequences, and 12
partial matches.
|