Nucleic Acids Research, 2001, Vol. 29, No. 18 3784-3795
© 2001 Oxford University Press
Survey and Summary |
AdoMet-dependent methylation, DNA methyltransferases and base flipping
Emory University School of Medicine, Department of Biochemistry, 1510 Clifton Road, Atlanta, GA 30322, USA and 1New England Biolabs, 32 Tozer Road, Beverly, MA 01915, USA
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 ß-sheet (6
7
5 4 1 2 3) 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 7). 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.
* To whom correspondence should be addressed. Tel: +1 404 727 8491; Fax: +1 404 727 3746; Email: xcheng{at}emory.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. L. Randall, L. Zechiedrich, and B. M. Pettitt In the absence of writhe, DNA relieves torsional stress with localized, sequence-dependent structural failure to preserve B-form Nucleic Acids Res., September 1, 2009; 37(16): 5568 - 5577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mura and J. A. McCammon Molecular dynamics of a {kappa}B DNA element: base flipping via cross-strand intercalative stacking in a microsecond-scale simulation Nucleic Acids Res., September 1, 2008; 36(15): 4941 - 4955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Carpenter and A. S. Bhagwat DNA base flipping by both members of the PspGI restriction-modification system Nucleic Acids Res., September 1, 2008; 36(16): 5417 - 5425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Coffin and N. O. Reich Modulation of Escherichia coli DNA Methyltransferase Activity by Biologically Derived GATC-flanking Sequences J. Biol. Chem., July 18, 2008; 283(29): 20106 - 20116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Daujotyte, Z. Liutkeviciute, G. Tamulaitis, and S. Klimasauskas Chemical mapping of cytosines enzymatically flipped out of the DNA helix Nucleic Acids Res., June 1, 2008; 36(10): e57 - e57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Youngblood, E. Bonnist, D. T.F. Dryden, A. C. Jones, and N. O. Reich Differential stabilization of reaction intermediates: specificity checkpoints for M.EcoRI revealed by transient fluorescence and fluorescence lifetime studies Nucleic Acids Res., May 1, 2008; 36(9): 2917 - 2925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. P. Jurkowski, N. Anspach, L. Kulishova, W. Nellen, and A. Jeltsch The M.EcoRV DNA-(Adenine N6)-methyltransferase Uses DNA Bending for Recognition of an Expanded EcoDam Recognition Site J. Biol. Chem., December 21, 2007; 282(51): 36942 - 36952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Walbott, S. Auxilien, H. Grosjean, and B. Golinelli-Pimpaneau The Carboxyl-terminal Extension of Yeast tRNA m5C Methyltransferase Enhances the Catalytic Efficiency of the Amino-terminal Domain J. Biol. Chem., August 10, 2007; 282(32): 23663 - 23671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Liebert, J. R. Horton, S. Chahar, M. Orwick, X. Cheng, and A. Jeltsch Two Alternative Conformations of S-Adenosyl-L-homocysteine Bound to Escherichia coli DNA Adenine Methyltransferase and the Implication of Conformational Changes in Regulating the Catalytic Cycle J. Biol. Chem., August 3, 2007; 282(31): 22848 - 22855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sunita, E. Purta, M. Durawa, K. L. Tkaczuk, J. Swaathi, J. M. Bujnicki, and J. Sivaraman Functional specialization of domains tandemly duplicated within 16S rRNA methyltransferase RsmC Nucleic Acids Res., July 26, 2007; 35(13): 4264 - 4274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tamulaitis, M. Zaremba, R. H. Szczepanowski, M. Bochtler, and V. Siksnys Nucleotide flipping by restriction enzymes analyzed by 2-aminopurine steady-state fluorescence Nucleic Acids Res., July 9, 2007; 35(14): 4792 - 4799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Reichow, T. Hamma, A. R. Ferre-D'Amare, and G. Varani The structure and function of small nucleolar ribonucleoproteins Nucleic Acids Res., March 12, 2007; 35(5): 1452 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. V. Lesnyak, J. Osipiuk, T. Skarina, P. V. Sergiev, A. A. Bogdanov, A. Edwards, A. Savchenko, A. Joachimiak, and O. A. Dontsova Methyltransferase That Modifies Guanine 966 of the 16 S rRNA: FUNCTIONAL IDENTIFICATION AND TERTIARY STRUCTURE J. Biol. Chem., February 23, 2007; 282(8): 5880 - 5887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Watanabe, H. Yuzawa, N. Handa, and I. Kobayashi Hyperthermophilic DNA Methyltransferase M.PabI from the Archaeon Pyrococcus abyssi Appl. Envir. Microbiol., August 1, 2006; 72(8): 5367 - 5375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mashhoon, C. Pruss, M. Carroll, P. H. Johnson, and N. O. Reich Selective Inhibitors of Bacterial DNA Adenine Methyltransferases J Biomol Screen, August 1, 2006; 11(5): 497 - 510. [Abstract] [PDF]
|
|
|
|
|
|
J. R. Horton, X. Zhang, R. Maunus, Z. Yang, G. G. Wilson, R. J. Roberts, and X. Cheng DNA nicking by HinP1I endonuclease: bending, base flipping and minor groove expansion Nucleic Acids Res., February 9, 2006; 34(3): 939 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Goll, F. Kirpekar, K. A. Maggert, J. A. Yoder, C.-L. Hsieh, X. Zhang, K. G. Golic, S. E. Jacobsen, and T. H. Bestor Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2 Science, January 20, 2006; 311(5759): 395 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Neely, D. Daujotyte, S. Grazulis, S. W. Magennis, D. T. F. Dryden, S. Klimasauskas, and A. C. Jones Time-resolved fluorescence of 2-aminopurine as a probe of base flipping in M.HhaI-DNA complexes Nucleic Acids Res., December 9, 2005; 33(22): 6953 - 6960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Macbeth, H. L. Schubert, A. P. VanDemark, A. T. Lingam, C. P. Hill, and B. L. Bass Inositol Hexakisphosphate Is Bound in the ADAR2 Core and Required for RNA Editing Science, September 2, 2005; 309(5740): 1534 - 1539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-J. Su, M. R. Tock, S. U. Egelhaaf, W. C. K. Poon, and D. T. F. Dryden DNA bending by M.EcoKI methyltransferase is coupled to nucleotide flipping Nucleic Acids Res., June 7, 2005; 33(10): 3235 - 3244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-O. Esteve, D. Patnaik, H. G. Chin, J. Benner, M. A. Teitell, and S. Pradhan Functional analysis of the N- and C-terminus of mammalian G9a histone H3 methyltransferase Nucleic Acids Res., June 6, 2005; 33(10): 3211 - 3223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Chrebet, D. Wisniewski, A. L. Perkins, Q. Deng, M. B. Kurtz, A. Marcy, and S. A. Parent Cell-Based Assays to Detect Inhibitors of Fungal mRNA Capping Enzymes and Characterization of Sinefungin as a Cap Methyltransferase Inhibitor J Biomol Screen, June 1, 2005; 10(4): 355 - 364. [Abstract] [PDF]
|
|
|
|
 |
|
 K. HART, B. NYSTROM, M. OHMAN, and L. NILSSON Molecular dynamics simulations and free energy calculations of base flipping in dsRNA RNA, May 1, 2005; 11(5): 609 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Merkiene and S. Klimasauskas Probing a rate-limiting step by mutational perturbation of AdoMet binding in the HhaI methyltransferase Nucleic Acids Res., January 13, 2005; 33(1): 307 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Hiley, J. Jackman, T. Babak, M. Trochesset, Q. D. Morris, E. Phizicky, and T. R. Hughes Detection and discovery of RNA modifications using microarrays Nucleic Acids Res., January 7, 2005; 33(1): e2 - e2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chandrashekaran, M. Saravanan, D. R. Radha, and V. Nagaraja Ca2+-mediated Site-specific DNA Cleavage and Suppression of Promiscuous Activity of KpnI Restriction Endonuclease J. Biol. Chem., November 26, 2004; 279(48): 49736 - 49740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zaleski and A. Piekarowicz Characterization of a dam mutant of Haemophilus influenzae Rd Microbiology, November 1, 2004; 150(11): 3773 - 3781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sawada, Z. Yang, J. R. Horton, R. E. Collins, X. Zhang, and X. Cheng Structure of the Conserved Core of the Yeast Dot1p, a Nucleosomal Histone H3 Lysine 79 Methyltransferase J. Biol. Chem., October 8, 2004; 279(41): 43296 - 43306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aittaleb, T. Visone, M. O. Fenley, and H. Li Structural and Thermodynamic Evidence for a Stabilizing Role of Nop5p in S-Adenosyl-L-methionine Binding to Fibrillarin J. Biol. Chem., October 1, 2004; 279(40): 41822 - 41829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tanaka, K. Tsumoto, Y. Yasutake, M. Umetsu, M. Yao, H. Fukada, I. Tanaka, and I. Kumagai How Oligomerization Contributes to the Thermostability of an Archaeon Protein: PROTEIN L-ISOASPARTYL-O-METHYLTRANSFERASE FROM SULFOLOBUS TOKODAII J. Biol. Chem., July 30, 2004; 279(31): 32957 - 32967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Horton, G. Ratner, N. K. Banavali, N. Huang, Y. Choi, M. A. Maier, V. E. Marquez, A. D. MacKerell Jr, and X. Cheng Caught in the act: visualization of an intermediate in the DNA base-flipping pathway induced by HhaI methyltransferase Nucleic Acids Res., July 23, 2004; 32(13): 3877 - 3886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. H. Cotton, B. Stoddard, and W. W. Parson Oxidative Inhibition of Human Soluble Catechol-O-methyltransferase J. Biol. Chem., May 28, 2004; 279(22): 23710 - 23718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Chen, J.-R. V. Lin, R. Darbha, P. Lin, T.-Y. Liu, and Y.-M. A. Chen Glycine N-Methyltransferase Tumor Susceptibility Gene in the Benzo(a)pyrene-Detoxification Pathway Cancer Res., May 15, 2004; 64(10): 3617 - 3623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Bujnicki, M. Feder, C. L. Ayres, and K. L. Redman Sequence-structure-function studies of tRNA:m5C methyltransferase Trm4p and its relationship to DNA:m5C and RNA:m5U methyltransferases Nucleic Acids Res., April 30, 2004; 32(8): 2453 - 2463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-J. Su, B. A. Connolly, C. Darlington, R. Mallin, and D. T. F. Dryden Unusual 2-aminopurine fluorescence from a complex of DNA and the EcoKI methyltransferase Nucleic Acids Res., April 23, 2004; 32(7): 2223 - 2230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. G. Kossykh and R. S. Lloyd A DNA Adenine Methyltransferase of Escherichia coli That Is Cell Cycle Regulated and Essential for Viability J. Bacteriol., April 1, 2004; 186(7): 2061 - 2067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Okuwaki and A. Verreault Maintenance DNA Methylation of Nucleosome Core Particles J. Biol. Chem., January 23, 2004; 279(4): 2904 - 2912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Osipiuk, M. A. Walsh, and A. Joachimiak Crystal structure of MboIIA methyltransferase Nucleic Acids Res., September 15, 2003; 31(18): 5440 - 5448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Galimand, P. Courvalin, and T. Lambert Plasmid-Mediated High-Level Resistance to Aminoglycosides in Enterobacteriaceae Due to 16S rRNA Methylation Antimicrob. Agents Chemother., August 1, 2003; 47(8): 2565 - 2571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Katz, M. Dlakic, and S. Clarke Automated Identification of Putative Methyltransferases from Genomic Open Reading Frames Mol. Cell. Proteomics, August 1, 2003; 2(8): 525 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Detich, S. Hamm, G. Just, J. D. Knox, and M. Szyf The Methyl Donor S-Adenosylmethionine Inhibits Active Demethylation of DNA: A CANDIDATE NOVEL MECHANISM FOR THE PHARMACOLOGICAL EFFECTS OF S-ADENOSYLMETHIONINE J. Biol. Chem., May 30, 2003; 278(23): 20812 - 20820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tamaru and E. U. Selker Synthesis of Signals for De Novo DNA Methylation in Neurospora crassa Mol. Cell. Biol., April 1, 2003; 23(7): 2379 - 2394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Daujotyte, G. Vilkaitis, L. Manelyte, J. Skalicky, T. Szyperski, and S. Klimasauskas Solubility engineering of the HhaI methyltransferase Protein Eng. Des. Sel., April 1, 2003; 16(4): 295 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Huang, N. K. Banavali, and A. D. MacKerell Jr. Protein-facilitated base flipping in DNA by cytosine-5-methyltransferase PNAS, January 7, 2003; 100(1): 68 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gowher and A. Jeltsch Molecular Enzymology of the Catalytic Domains of the Dnmt3a and Dnmt3b DNA Methyltransferases J. Biol. Chem., May 31, 2002; 277(23): 20409 - 20414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-c. Huang, C. V. Smith, M. S. Glickman, W. R. Jacobs Jr., and J. C. Sacchettini Crystal Structures of Mycolic Acid Cyclopropane Synthases from Mycobacterium tuberculosis J. Biol. Chem., March 22, 2002; 277(13): 11559 - 11569. [Abstract] [Full Text] [PDF]
|
|