Zebularine: A novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases

Journal of Molecular Biology

Volumn 321, Issue 4, 2002, Pages 591-599

  Zhou, L ^a   Cheng, X ^a   Connolly, B A ^b   Dickman, M J ^c   Hurd, P J ^d   Hornby, D P ^c  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

^c UNIVERSITY OF SHEFFIELD   (United Kingdom)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Base flipping; DNA methylation; DNA methyltransferase; M.Hha I; Zebularine

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; CYTOSINE; DNA METHYLTRANSFERASE; FLUCYTOSINE DEOXYRIBOSIDE; ZEBULARINE;

ARTICLE; BINDING AFFINITY; COVALENT BOND; DNA DRUG COMPLEX; DNA METHYLATION; DNA STRUCTURE; DRUG DNA BINDING; DRUG EFFECT; DRUG MECHANISM; DRUG PROTEIN BINDING; ENZYME INHIBITION; HAEMOPHILUS; NONHUMAN; PRIORITY JOURNAL; X RAY CRYSTALLOGRAPHY;

HAEMOPHILUS HAEMOLYTICUS;

EID: 0036965821     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0022-2836(02)00676-9     Document Type: Article

References (38)

1. Bestor, T. H. (1998). Gene silencing. Methylation meets acetylation. Nature, 393, 311-312.
2. Jones, P. A. & Takai, D. (2001). The role of DNA methylation in mammalian epigenetics. Science, 293, 1068-1070.
3. Bestor, T. H. (2000). The DNA methyltransferases of mammals. Hum. Mol. Genet. 16, 2395-2402.
4. Redaschi, N. & Bickle, T. A. (1996). DNA restriction and modification systems. In Escherichia coli and Salmonella: Cellular and Molecular Biology (Neidhart, F. C., Curtiss, R. III, Ingraham, J. L., Brooks Low, K. B., Magasanik, B., Reznikoff, W. S., Riley, R., Schaecter, M. & Umbarger, H. E., eds), 2nd edit., pp. 773-781, ASM Press, Washington, DC.
5. Bestor, T. H. & Verdine, G. L. (1994). DNA Methyltransferases. Curr. Opin. Cell. Biol. 6, 380-389.
6. Rountree, M. R., Bachman, K. E., Herman, J. G. & Baylin, S. B. (2001). DNA methylation, chromatin inheritance, and cancer. Oncogene, 20, 3156-3165.
7. Cheng, X. (1995). Structure and function of DNA methyltransferases. Annu. Rev. Biophys. Biomol. Struct. 24, 293-318.
8. Dong, A., Yoder, J. A., Zhang, X., Zhou, L., Bestor, T. H. & Cheng, X. (2001). Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA. Nucl. Acids Res. 29, 439-448.
9. Cheng, X. & Roberts, R. J. (2001). AdoMet-dependent methylation, DNA methyltransferases and base flipping. Nucl. Acids Res. 29, 3784-3795.
10. Jones, P. A. & Taylor, S. M. (1980). Cellular differentiation, cytidine analogs and DNA methylation. Cell, 20, 85-93.
11. Santi, D. V., Garrett, C. E. & Barr, P. J. (1983). On the mechanism of inhibition of DNA-cytosine methyltransferases by cytosine analogs. Cell, 33, 9-10.
12. Sheikhnejad, G., Brank, A., Christman, J. K., Goddard, A., Alvarez, E., Ford, H., Jr et al. (1999). Mechanism of inhibition of DNA (cytosine C5)-methyltransferases by oligodeoxyribonucleotides containing 5,6-dihydro-5-AzaCytosine. J. Mol. Biol. 285, 2021-2034.
13. Kumar, S., Horton, J. R., Jones, G. D., Walker, R. T., Roberts, R. J. & Cheng, X. (1997). DNA containing 4′-thio-2′-deoxycytidine inhibits methylation by HhaI methyltransferase. Nucl. Acids Res. 25, 2773-2783.
14. Chen, L., MacMillan, A. M., Chang, W., Ezaz-Nikpay, K., Lane, W. S. & Verdine, G. L. (1991). Direct identification of the active-site nucleophile in a DNA (cytosine-5)-methyltransferase. Biochemistry, 30, 11018-11025.
15. Klimasauskas, S., Kumar, S., Roberts, R. J. & Cheng, X. (1994). HhaI methyltransferase flips its target base out of the DNA helix. Cell, 76, 357-369.
16. Wu, J. C. & Santi, D. V. (1987). Kinetic and catalytic mechanism of HhaI methyltransferase. J. Biol. Chem. 262, 4778-4786.
17. Baker, D. J., Kan, J. L. C. & Smith, S. S. (1988). Recognition of structural perturbations in DNA by human DNA(cytosine-5)methyltransferase. Gene, 74, 207-210.
18. Smith, S. S., Kan, J. L. C., Baker, D. J., Kaplan, B. E. & Dembek, P. (1991). Recognition of unusual DNA structures by human DNA(cytosine-5)methyltransferase. J. Mol. Biol. 217, 39-51.
19. Gabbara, S., Sheluho, D. & Bhagwat, A. S. (1995). Cytosine methyltransferase from Escherichia coli in which active site cysteine is replaced with serine is partially active. Biochemistry, 34, 8914-8923.
20. Gabbara, S. & Bhagwat, A. S. (1995). The mechanism of inhibition of DNA (cytosine-5-)-methyltransferases by 5-azacytosine is likely to involve methyltransfer to the inhibitor. Biochem. J. 307, 87-92.
21. Santi, D. V., Norment, A. & Garrett, C. E. (1984). Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-AzaCytosine. Proc. Natl Acad. Sci. USA, 81, 6993-6997.
22. Jackson-Grusby, L., Laird, P. W., Magge, S. N., Moeller, B. J. & Jaenisch, R. (1997). Mutagenicity of 5-aza-2′-deoxycytidine is mediated by the mammalian DNA methyltransferase. Proc. Natl Acad. Sci. USA, 94, 4681-4685.
23. Taylor, C., Ford, K., Connolly, B. A. & Hornby, D. P. (1993). Determination of the order of substrate addition to MspI DNA methyltransferase using a novel mechanism-based inhibitor. Biochem. J. 291, 493-504.
24. Hurd, P. J., Whitmarsh, A. J., Baldwin, G. S., Kelly, S. M., Waltho, J. P., Price, N. C. et al. (1999). Mechanism-based inhibition of C5-cytosine DNA methyltransferases by 2-H pyrimidinone. J. Mol. Biol. 286, 389-401.
25. Baldwin, G. S., Kelly, S. M., Price, N. C., Wilson, G. W., Connolly, B. A., Artymiuk, P. J. & Hornby, D. P. (1994). Ligand-induced conformational states of the cytosine-specific DNA methyltransferase M.HgaI-2. J. Mol. Biol. 235, 545-553.
26. Saenger, W. (1984). Principles of Nucleic Acid Structure, Springer, New York.
27. Frick, L., Yang, C., Marquez, V. E. & Wolfenden, R. (1989). Binding of pyrimidin-2-one ribonucleoside by cytidine deaminase as the transition state analogue 3,4 dihydrouridine and the contribution of the 4-hydroxyl group to its binding affinity. Biochemistry, 28, 9423-9430.
28. Betts, L., Xiang, S., Short, S. A., Wolfenden, R. & Carter, C. W., Jr (1994). Cytidine deaminase. The 2.3 Å crystal structure of an enzyme: transition state analogue complex. J. Mol. Biol. 235, 635-656.
29. Smith, S. S., Hardy, T. A. & Baker, D. J. (1987). Human DNA (cytosine-5) methyltransferase selectively methylates duplex DNA containing mispairs. Nucl. Acids Res. 15, 6899-6916.
30. Klimasauskas, S. & Roberts, R. J. (1995). M.Hha I binds tightly to substrates containing mismatches at the target base. Nucl. Acids Res. 23, 1388-1395.
31. Yang, A. S., Shen, J. C., Zingg, J. M., Mi, S. & Jones, P. A. (1995). HhaI and HpaII DNA methyl-transferases bind DNA mismatches, methylate uracil and block DNA repair. Nucl. Acids Res. 23, 1380-1387.
32. Sharath, A., Weinhold, E. & Bhagwat, A. S. (2000). Reviving a dead enzyme. Cytosine deamination promoted by an inactive DNA methyltransferase and an S-adenosylmethionine analogue. Biochemistry, 39, 14611-14616.
33. Jeong, L. S., Buenger, G., McCormack, J., Cooney, D. A., Hao, Z. & Marquez, V. E. (1998). Carbocyclic analogues of the potent cytidine deaminase inhibitor 1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine). J. Med. Chem. 41, 2572-2578.
34. Connolly, B. A. & Newman, P. C. (1989). Synthesis and properties of oligonucleotides containing 4-thiothymidine, 5-methyl-2-pyrimidinone-1-β-D(2′-deoxyriboside) and 2-thiothymidine. Nucl. Acids Res. 17, 4957-4974.
35. Brünger, A. T. (1992). X-PLOR. A system for X-ray crystallography and NMR, version 3.1, Yale University, New Haven, CT.
36. O'Gara, M., Klimasauskas, S., Roberts, R. J. & Cheng, X. (1996). Enzymatic C5-cytosine methylation of DNA: mechanistic implications of new crystal structures for HhaI methyltransferase-DNA-AdoHcy complexes. J. Mol. Biol. 261, 634-645.
37. Smith, S. S., Niu, L., Baker, D. J., Wendel, J. A., Kane, S. E. & Joy, D. S. (1997). Nucleoprotein-based nanoscaleassembly. Proc. Natl Acad. Sci. USA, 94, 2162-2167.
38. Hurd, P. J. (1996). A study of the catalytic properties of M.Msp I DNA methyltransferase, PhD thesis, University of Sheffield, UK