title: Enzymatic deamination of the epigenetic base N-6-methyladenine.
abstract: Two enzymes of unknown function from the amidohydrolase superfamily were discovered to catalyze the deamination of N-6-methyladenine to hypoxanthine and methyl amine. The methylation of adenine in bacterial DNA is a common modification for the protection of host DNA against restriction endonucleases. The enzyme from Bacillus halodurans, Bh0637, catalyzes the deamination of N-6-methyladenine with a k(cat) of 185 s(-1) and a k(cat)/K(m) of 2.5 × 10(6) M(-1) s(-1). Bh0637 catalyzes the deamination of N-6-methyladenine 2 orders of magnitude faster than adenine. A comparative model of Bh0637 was computed using the three-dimensional structure of Atu4426 (PDB code: 3NQB) as a structural template and computational docking was used to rationalize the preferential utilization of N-6-methyladenine over adenine. This is the first identification of an N-6-methyladenine deaminase (6-MAD).
authors.affiliation: Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012, United States.
authors.forename: Siddhesh S
authors.initials: SS
authors.lastname: Kamat
authors.forename: Hao
authors.initials: H
authors.lastname: Fan
authors.forename: J Michael
authors.initials: JM
authors.lastname: Sauder
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Burley
authors.forename: Brian K
authors.initials: BK
authors.lastname: Shoichet
authors.forename: Andrej
authors.initials: A
authors.lastname: Sali
authors.forename: Frank M
authors.initials: FM
authors.lastname: Raushel
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D000581:Amidohydrolases / Q000737:chemistry*; D003641:Deamination; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D013379:Substrate Specificity
chemical_list: D000225:Adenine; D000581:Amidohydrolases; C000730567:6-methyladenine