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Publication Abstract from PubMed

DNA N6-methyladenine modification plays an important role in regulating a variety of biological functions in bacteria. However, the mechanism of sequence-specific recognition in N6-methyladenine modification remains elusive. M1.HpyAVI, a DNA N6-adenine methyltransferase from Helicobacter pylori, shows more promiscuous substrate specificity than other enzymes. Here, we present the crystal structures of cofactor-free and AdoMet-bound structures of this enzyme, which were determined at resolutions of 3.0 A and 3.1 A, respectively. The core structure of M1.HpyAVI resembles the canonical AdoMet-dependent MTase fold, while the putative DNA binding regions considerably differ from those of the other MTases, which may account for the substrate promiscuity of this enzyme. Site-directed mutagenesis experiments identified residues D29 and E216 as crucial amino acids for cofactor binding and the methyl transfer activity of the enzyme, while P41, located in a highly flexible loop, playing a determinant role for substrate specificity. Taken together, our data revealed the structural basis underlying DNA N6-adenine methyltransferase substrate promiscuity.

Biochemical and structural characterization of a DNA N6-adenine methyltransferase from Helicobacter pylori.,Ma B, Ma J, Liu D, Guo L, Chen H, Ding J, Liu W, Zhang H Oncotarget. 2016 Jul 5;7(27):40965-40977. doi: 10.18632/oncotarget.9692. PMID:27259995^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.