We have determined the structure of Pvu II methyltransferase (M. Pvu II) 
complexed with S -adenosyl-L-methionine (AdoMet) by multiwavelength anomalous 
diffraction, using a crystal of the selenomethionine-substituted protein. M. Pvu 
II catalyzes transfer of the methyl group from AdoMet to the exocyclic amino 
(N4) nitrogen of the central cytosine in its recognition sequence 5'-CAGCTG-3'. 
The protein is dominated by an open alpha/beta-sheet structure with a prominent 
V-shaped cleft: AdoMet and catalytic amino acids are located at the bottom of 
this cleft. The size and the basic nature of the cleft are consistent with 
duplex DNA binding. The target (methylatable) cytosine, if flipped out of the 
double helical DNA as seen for DNA methyltransferases that generate 
5-methylcytosine, would fit into the concave active site next to the AdoMet. 
This M. Pvu IIalpha/beta-sheet structure is very similar to those of M. Hha I (a 
cytosine C5 methyltransferase) and M. Taq I (an adenine N6 methyltransferase), 
consistent with a model predicting that DNA methyltransferases share a common 
structural fold while having the major functional regions permuted into three 
distinct linear orders. The main feature of the common fold is a seven-stranded 
beta-sheet (6 7 5 4 1 2 3) formed by five parallel beta-strands and an 
antiparallel beta-hairpin. The beta-sheet is flanked by six parallel 
alpha-helices, three on each side. The AdoMet binding site is located at the 
C-terminal ends of strands beta1 and beta2 and the active site is at the 
C-terminal ends of strands beta4 and beta5 and the N-terminal end of strand 
beta7. The AdoMet-protein interactions are almost identical among M. Pvu II, M. 
Hha I and M. Taq I, as well as in an RNA methyltransferase and at least one 
small molecule methyltransferase. The structural similarity among the active 
sites of M. Pvu II, M. Taq I and M. Hha I reveals that catalytic amino acids 
essential for cytosine N4 and adenine N6 methylation coincide spatially with 
those for cytosine C5 methylation, suggesting a mechanism for amino methylation.