Specificity in protein-DNA interactions: energetic recognition by the (cytosine-C5)-methyltransferase from HhaI.

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TitleSpecificity in protein-DNA interactions: energetic recognition by the (cytosine-C5)-methyltransferase from HhaI.
Publication TypeJournal Article
Year of Publication2005
AuthorsHuang, N, Mackerell, AD
JournalJ Mol Biol
Volume345
Issue2
Pagination265-74
Date Published2005 Jan 14
ISSN0022-2836
KeywordsCrystallography, X-Ray, Deoxyribonucleases, Type II Site-Specific, DNA, Hydrogen Bonding, Models, Molecular, Nucleic Acid Conformation, Protein Binding, Protein Conformation, Software, Thermodynamics
Abstract

Sequence-specific interactions between proteins and DNA are essential for a variety of biological functions. The (cytosine-C5)-methyltransferase from HhaI (M.HhaI) specifically modifies the second base in GCGC sequences, employing a base flipping mechanism to access the target base being chemically modified. The mechanism of sequence-specific recognition of M.HhaI is not evident based on crystallographic structures, leading to the suggestion that recognition is linked to the flipping event itself, a process that may be referred to as energetic recognition. Using computational methods, it is shown that the free energy barriers to flipping are significantly higher in non-cognate versus the cognate sequence, supporting the energetic recognition mechanism. Energetic recognition is imparted by two protein "selectivity filters" that function via a "web" of protein-DNA interactions in short-lived, high energy states present along the base flipping pathway. Other sequence-specific DNA binding proteins whose function involves significant distortion of DNA's conformation may use a similar recognition mechanism.

DOI10.1016/j.jmb.2004.10.042
Alternate JournalJ. Mol. Biol.
PubMed ID15571720
Grant ListGM 51501 / GM / NIGMS NIH HHS / United States