Low-frequency normal mode in DNA HhaI methyltransferase and motions of residues involved in the base flipping

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Low-frequency normal mode in DNA HhaI methyltransferase and motions of residues involved in the base flipping.

The results of normal-mode analyses are in accord with the proposal that a low-frequency motion of the HhaI methyltransferase enzyme is responsible for base flipping in bound DNA. The vectors of the low-frequency normal mode of residues Ser-85 and Ile-86 point directly to the phosphate and ribose moieties of the DNA backbone near the target base in position to rotate the dihedral angles and fli...

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Mutational analysis of conserved residues in HhaI DNA methyltransferase.

HhaI DNA methyltransferase belongs to the C5-cytosine methyltransferase family, which is characterized by the presence of a set of highly conserved amino acids and motifs present in an invariant order. HhaI DNA methyltransferase has been subjected to a lot of biochemical and crystallographic studies. A number of issues, especially the role of the conserved amino acids in the methyltransferase a...

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Caught in the act: visualization of an intermediate in the DNA base-flipping pathway induced by HhaI methyltransferase.

Rotation of a DNA or RNA nucleotide out of the double helix and into a protein pocket ('base flipping') is a mechanistic feature common to some DNA/RNA-binding proteins. Here, we report the structure of HhaI methyltransferase in complex with DNA containing a south-constrained abasic carbocyclic sugar at the target site in the presence of the methyl donor byproduct AdoHcy. Unexpectedly, the lock...

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Metadynamics Simulation Study on the Conformational Transformation of HhaI Methyltransferase: An Induced-Fit Base-Flipping Hypothesis

DNA methyltransferases play crucial roles in establishing and maintenance of DNA methylation, which is an important epigenetic mark. Flipping the target cytosine out of the DNA helical stack and into the active site of protein provides DNA methyltransferases with an opportunity to access and modify the genetic information hidden in DNA. To investigate the conversion process of base flipping in ...

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Water-assisted dual mode cofactor recognition by HhaI DNA methyltransferase.

Energetically competent binary recognition of the cofactor S-adenosyl-L-methionine (AdoMet) and the product S-adenosyl-L-homocysteine (AdoHcy) by the DNA (cytosine C-5) methyltransferase (M.HhaI) is demonstrated herein. Titration calorimetry reveals a dual mode, involving a primary dominant exothermic reaction followed by a weaker endothermic one, for the recognition of AdoMet and AdoHcy by M.H...

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ژورنال

عنوان ژورنال: Proceedings of the National Academy of Sciences

سال: 2005

ISSN: 0027-8424,1091-6490

DOI: 10.1073/pnas.0507913102