Crystal structure of a putative DNA methylase TTHA0409 from <i>Thermus thermophilus</i> HB8

Morita, R; Ishikawa, H.; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

doi:10.1002/prot.22158

Cited by 10 publications

(7 citation statements)

References 37 publications

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“…M1.MboII, from Moraxella bovis (Figure 3D ), methylates the 3′ adenine of an asymmetric sequence 5′-GAAG A -3′, and the homodimeric structure again supported by biochemical results ( 65 ). Dimer formation was also observed in structures for THA0409 from Thermus thermophilus HB8 (Figure 3E ) ( 66 ) and M1.HpyAVI from Helicobacter pylori (Figure 3F ) ( 67 ). Furthermore, even where structures do not yet exist, there is biochemical evidence for dimerization in several other class β MTases (M.BamHI ( 68 ), M.LiaCI ( 69 ), M.KpnI ( 70 , 71 ), M.HpyAXVII ( 72 )).…”

Section: Introductionmentioning

confidence: 68%

Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences

Woodcock

Horton

Zhang

et al. 2020

Nucleic Acids Research

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S-adenosyl-l-methionine dependent methyltransferases catalyze methyl transfers onto a wide variety of target molecules, including DNA and RNA. We discuss a family of methyltransferases, those that act on the amino groups of adenine or cytosine in DNA, have conserved motifs in a particular order in their amino acid sequence, and are referred to as class beta MTases. Members of this class include M.EcoGII and M.EcoP15I from Escherichia coli, Caulobacter crescentus cell cycle–regulated DNA methyltransferase (CcrM), the MTA1-MTA9 complex from the ciliate Oxytricha, and the mammalian MettL3-MettL14 complex. These methyltransferases all generate N6-methyladenine in DNA, with some members having activity on single-stranded DNA as well as RNA. The beta class of methyltransferases has a unique multimeric feature, forming either homo- or hetero-dimers, allowing the enzyme to use division of labor between two subunits in terms of substrate recognition and methylation. We suggest that M.EcoGII may represent an ancestral form of these enzymes, as its activity is independent of the nucleic acid type (RNA or DNA), its strandedness (single or double), and its sequence (aside from the target adenine).

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Section: Introductionmentioning

confidence: 68%

Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences

Woodcock

Horton

Zhang

et al. 2020

Nucleic Acids Research

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“…For instance, M.DpnII, M.RsrI, M.KpnI, and M.MboIIA have been found as dimers in solution [12, 24]. In addition, several MTases including M.MboIIA, M.RsrI and TTH0409 form tightly associated dimers in crystal structures [2, 15, 25]. Nonetheless, some DNA MTases such as M.CcrMI and the Bacillus amyloliquefaciens MTase dissociate from dimer into monomer upon DNA-binding [2].…”

Section: Resultsmentioning

confidence: 99%

“…Structural comparison between M1.HpyAVI and a putative β-class N 4 cytosine MTase named TTHA0409 (PDB ID 2ZIF) [25] showed a good similarity as well, giving an RMSD of 1.73 Å on 164 C α atoms (Figure 3D). Exactly like the above comparison, the most significant difference exists in the TRD, where the structures vary in terms of length and presence of α-helices (Figure S1).…”

Section: Resultsmentioning

confidence: 99%

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

Liu

et al. 2016

Oncotarget

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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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“…They do contain the DNA binding domain with the conserved Arg and Tyr residues (Figure 1). ATL proteins have been characterized from E. coli, 234,235 Vibrio parahemolyticus, 236 S. pombe, 234,235,237 Thermus thermophilus, 238,239 and the starlet sea anemone Nematostella vectensis (Kanugula, S., and Pegg, A. E., unpublished work).…”

Section: Bridge To Other Dna Repair Pathways and Transcriptionmentioning

confidence: 99%

Multifaceted Roles of Alkyltransferase and Related Proteins in DNA Repair, DNA Damage, Resistance to Chemotherapy, and Research Tools

Pegg

2011

Chem. Res. Toxicol.

189

255

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O6-Alkylguanine-DNA alkyltransferase (AGT) is a widely distributed, unique DNA repair protein that acts as a single agent to directly remove alkyl groups located on the O6-position of guanine from DNA restoring the DNA in one step. The protein acts only once and its alkylated form is degraded rapidly. It is a major factor in counteracting the mutagenic, carcinogenic and cytotoxic effects of agents that form such adducts including N-nitroso-compounds and a number of cancer chemotherapeutics. This review describes the structure, function and mechanism of action of AGTs and of a family of related alkyltransferase-like proteins, which do not alone act to repair O6-alkylguanines in DNA but link repair to other pathways. The paradoxical ability of AGTs to stimulate the DNA-damaging ability of dihaloalkanes and other bis-electrophiles via the formation of AGT-DNA crosslinks is also described. Other important properties of AGTs include the ability to provide resistance to cancer therapeutic alkylating agents and the availability of AGT inhibitors such as O6-benzylguanine that might overcome this resistance is discussed. Finally, the properties of fusion proteins in which AGT sequences are linked to other proteins are outlined. Such proteins occur naturally and synthetic variants engineered to react specifically with derivatives of O6-benzylguanine are the basis of a valuable research technique for tagging proteins with specific reagents.

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Crystal structure of a putative DNA methylase TTHA0409 from Thermus thermophilus HB8

Cited by 10 publications

References 37 publications

Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences

Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences

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

Multifaceted Roles of Alkyltransferase and Related Proteins in DNA Repair, DNA Damage, Resistance to Chemotherapy, and Research Tools

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