1mht
COVALENT TERNARY STRUCTURE OF HHAI METHYLTRANSFERASE, DNA AND S-ADENOSYL-L-HOMOCYSTEINECOVALENT TERNARY STRUCTURE OF HHAI METHYLTRANSFERASE, DNA AND S-ADENOSYL-L-HOMOCYSTEINE
Structural highlights
FunctionMTH1_HAEPH This methylase recognizes the double-stranded sequence GCGC, causes specific methylation on C-2 on both strands, and protects the DNA from cleavage by the HhaI endonuclease. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe crystal structure has been determined at 2.8 A resolution for a chemically-trapped covalent reaction intermediate between the HhaI DNA cytosine-5-methyltransferase, S-adenosyl-L-homocysteine, and a duplex 13-mer DNA oligonucleotide containing methylated 5-fluorocytosine at its target. The DNA is located in a cleft between the two domains of the protein and has the characteristic conformation of B-form DNA, except for a disrupted G-C base pair that contains the target cytosine. The cytosine residue has swung completely out of the DNA helix and is positioned in the active site, which itself has undergone a large conformational change. The DNA is contacted from both the major and the minor grooves, but almost all base-specific interactions between the enzyme and the recognition bases occur in the major groove, through two glycine-rich loops from the small domain. The structure suggests how the active nucleophile reaches its target, directly supports the proposed mechanism for cytosine-5 DNA methylation, and illustrates a novel mode of sequence-specific DNA recognition. HhaI methyltransferase flips its target base out of the DNA helix.,Klimasauskas S, Kumar S, Roberts RJ, Cheng X Cell. 1994 Jan 28;76(2):357-69. PMID:8293469[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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