Structure of RsrI methyltransferase, a member of the N6-adenine beta classof DNA methyltransferases

DNA methylation is important in cellular, developmental and disease process es, as well as in bacterial restriction-modification systems. Methylation o f DNA at the amino groups of cytosine and adenine is a common mode of prote ction against restriction endonucleases afforded by the bacterial methyltra nsferases. The first structure of an N6-adenine methyltransferase belonging to the beta class of bacterial methyltransferases is described here. The s tructure of M . Rsrl from Rhodobacter sphaeroides, which methylates the sec ond adenine of the GAATTC sequence, was determined to 1.75 Angstrom resolut ion using X-ray crystallography, Like other methyltransferases, the enzyme contains the methylase fold and has well-defined substrate binding pockets, The catalytic core most closely resembles the Pvull methyltransferase, a c ytosine amino methyltransferase of the same beta group, The larger nucleoti de binding pocket observed in M . Rsrl is expected because it methylates ad enine, However, the most striking difference between the Rsrl methyltransfe rase and the other bacterial enzymes is the structure of the putative DNA t arget recognition domain, which is formed in part by two helices on an exte nded arm of the protein on the face of the enzyme opposite the active site. This observation suggests that a dramatic conformational change or oligome rization may take place during DNA binding and methylation.