title: Structure of RsrI methyltransferase, a member of the N6-adenine beta class of DNA methyltransferases.
abstract: DNA methylation is important in cellular, developmental and disease processes, as well as in bacterial restriction-modification systems. Methylation of DNA at the amino groups of cytosine and adenine is a common mode of protection against restriction endonucleases afforded by the bacterial methyltransferases. The first structure of an N:6-adenine methyltransferase belonging to the beta class of bacterial methyltransferases is described here. The structure of M. RSR:I from Rhodobacter sphaeroides, which methylates the second adenine of the GAATTC sequence, was determined to 1.75 A resolution 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 PVU:II methyltransferase, a cytosine amino methyltransferase of the same beta group. The larger nucleotide binding pocket observed in M. RSR:I is expected because it methylates adenine. However, the most striking difference between the RSR:I methyltransferase and the other bacterial enzymes is the structure of the putative DNA target recognition domain, which is formed in part by two helices on an extended arm of the protein on the face of the enzyme opposite the active site. This observation suggests that a dramatic conformational change or oligomerization may take place during DNA binding and methylation.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Scavetta
authors.forename: C B
authors.initials: CB
authors.lastname: Thomas
authors.forename: M A
authors.initials: MA
authors.lastname: Walsh
authors.forename: S
authors.initials: S
authors.lastname: Szegedi
authors.forename: A
authors.initials: A
authors.lastname: Joachimiak
authors.forename: R I
authors.initials: RI
authors.lastname: Gumport
authors.forename: M E
authors.initials: ME
authors.lastname: Churchill
mesh_terms: D000225:Adenine / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D015257:DNA-Cytosine Methylases / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012242:Rhodobacter sphaeroides / Q000201:enzymology*; D012436:S-Adenosylmethionine / Q000378:metabolism; D016415:Sequence Alignment; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004268:DNA-Binding Proteins; D009711:Nucleotides; D012436:S-Adenosylmethionine; D004247:DNA; C020098:DNA modification methylase EcoRI; C047084:DNA modification methylase PvuII; D015257:DNA-Cytosine Methylases; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D000225:Adenine