AdoMet-dependent methylation, DNA methyltransferases and base flipping
- 15 September 2001
- journal article
- review article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 29 (18) , 3784-3795
- https://doi.org/10.1093/nar/29.18.3784
Abstract
Twenty AdoMet-dependent methyltransferases (MTases) have been characterized structurally by X-ray crystallography and NMR. These include seven DNA MTases, five RNA MTases, four protein MTases and four small molecule MTases acting on the carbon, oxygen or nitrogen atoms of their substrates. The MTases share a common core structure of a mixed seven-stranded beta-sheet (6 downward arrow 7 upward arrow 5 downward arrow 4 downward arrow 1 downward arrow 2 downward arrow 3 downward arrow) referred to as an 'AdoMet-dependent MTase fold', with the exception of a protein arginine MTase which contains a compact consensus fold lacking the antiparallel hairpin strands (6 downward arrow 7 upward arrow). The consensus fold is useful to identify hypothetical MTases during structural proteomics efforts on unannotated proteins. The same core structure works for very different classes of MTase including those that act on substrates differing in size from small molecules (catechol or glycine) to macromolecules (DNA, RNA and protein). DNA MTases use a 'base flipping' mechanism to deliver a specific base within a DNA molecule into a typically concave catalytic pocket. Base flipping involves rotation of backbone bonds in double-stranded DNA to expose an out-of-stack nucleotide, which can then be a substrate for an enzyme-catalyzed chemical reaction. The phenomenon is fully established for DNA MTases and for DNA base excision repair enzymes, and is likely to prove general for enzymes that require access to unpaired, mismatched or damaged nucleotides within base-paired regions in DNA and RNA. Several newly discovered MTase families in eukaryotes (DNA 5mC MTases and protein arginine and lysine MTases) offer new challenges in the MTase field.Keywords
This publication has 98 references indexed in Scilit:
- Recombinant Human DNA (Cytosine-5) MethyltransferaseJournal of Biological Chemistry, 1999
- Active site dynamics of the HhaI methyltransferase: insights from computer simulationJournal of Molecular Biology, 1999
- Structure of a binary complex of HhaI methyltransferase with S-adnosyl-l-methionine formed in the presence of a short non-specific DNA oligonucleotideJournal of Molecular Biology, 1999
- DNA Distortion and Base Flipping by the EcoRV DNA MethyltransferasePublished by Elsevier ,1997
- Enzymatic C5-Cytosine Methylation of DNA: Mechanistic Implications of New Crystal Structures forHhaI Methyltransferase-DNA-AdoHcy ComplexesJournal of Molecular Biology, 1996
- Targeted Base Stacking Disruption by the EcoRI DNA MethyltransferaseBiochemistry, 1996
- Structure-guided Analysis Reveals Nine Sequence Motifs Conserved among DNA Amino-methyl-transferases, and Suggests a Catalytic Mechanism for these EnzymesJournal of Molecular Biology, 1995
- Targeted mutation of the DNA methyltransferase gene results in embryonic lethalityPublished by Elsevier ,1992
- Cloning, over-expression and the catalytic properties of the EcoP15 modification methylase from Escherichia coliJournal of Molecular Biology, 1989
- Cleavage and methylation of DNA by the restriction endonuclease HinfIII isolated from Haemophilus influenzae RfJournal of Molecular Biology, 1980