Research Papers: Immunology:

Biochemical and structural characterization of a DNA N6-adenine methyltransferase from Helicobacter pylori

Bo Ma, Ji Ma, Dong Liu, Ling Guo, Huiling Chen, Jingjin Ding, Wei Liu and Hongquan Zhang _

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Oncotarget. 2016; 7:40965-40977. https://doi.org/10.18632/oncotarget.9692

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Bo Ma1, Ji Ma1, Dong Liu2, Ling Guo2, Huiling Chen2, Jingjin Ding3, Wei Liu2 and Hongquan Zhang1

1 Department of Human Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, China

2 Institute of Immunology, The Third Military Medical University, Chongqing, China

3 Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

Correspondence to:

Hongquan Zhang, email:

Wei Liu, email:

Keywords: DNA N6-adenine methyltransferase; M1.HpyAVI; substrate recognition; AdoMet-binding; Helicobacter pylori; Immunology and Microbiology Section; Immune response; Immunity

Received: January 29, 2016 Accepted: May 17, 2016 Published: May 29, 2016


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 Å and 3.1 Å, 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.

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