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

被引:11
|
作者
Ma, Bo [1 ,2 ]
Ma, Ji [1 ,2 ]
Liu, Dong [3 ]
Guo, Ling [3 ]
Chen, Huiling [3 ]
Ding, Jingjin [4 ]
Liu, Wei [3 ]
Zhang, Hongquan [1 ,2 ]
机构
[1] Peking Univ, Hlth Sci Ctr, Dept Human Anat Histol & Embryol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing, Peoples R China
[2] Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Beijing, Peoples R China
[3] Third Mil Med Univ, Inst Immunol, Chongqing, Peoples R China
[4] Chinese Acad Sci, Inst Biophys, Beijing, Peoples R China
基金
中国国家自然科学基金; 北京市自然科学基金;
关键词
DNA N6-adenine methyltransferase; M1.HpyAVI; substrate recognition; AdoMet-binding; RESTRICTION-MODIFICATION SYSTEMS; CRYSTAL-STRUCTURE; ADENINE METHYLATION; N-6-METHYLADENINE; EVOLUTION; SEQUENCE; CYTOSINE; MOTIFS; BASE;
D O I
10.18632/oncotarget.9692
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
DNA N-6-methyladenine modification plays an important role in regulating a variety of biological functions in bacteria. However, the mechanism of sequence-specific recognition in N-6-methyladenine modification remains elusive. M1.HpyAVI, a DNA N-6-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 angstrom and 3.1 angstrom, 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 N-6-adenine methyltransferase substrate promiscuity.
引用
收藏
页码:40965 / 40977
页数:13
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