DNA enzymes

Current Opinion in Chemical Biology

Volumn 2, Issue 6, 1998, Pages 680-687

  Sen, Dipankar ^a   Geyer, C Ronald ^b  

^a SIMON FRASER UNIVERSITY   (Canada)

^b The Molecular Sciences Institute   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; PORPHYRIN; RIBOZYME; RNA;

METABOLISM; REVIEW;

DNA; PORPHYRINS; RNA; RNA, CATALYTIC;

EID: 0032253390     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1367-5931(98)80103-8     Document Type: Article

References (52)

1. Breaker RR, Joyce GF: A DNA enzyme that cleaves RNA. Chem Biol 1994, 1:223-229.
2. Cuenoud B, Szostak JW: A DNA metalloenzyme with ligase activity. Nature 1995, 375:611-614.
3. 2+-dependent RNA phosphodiesterase activity. Chem Biol 1995, 2:655-660.
4. Li Y, Sen D: A catalytic DNA for porphyrin metallation. Nat Struct Biol 1996, 3:743-747.
5. Chartrand P, Harvey SC, Ferbeyre G, Usman N, Cedergren R: An oligodeoxyribonucleotide that supports catalytic activity in the hammerhead ribozyme domain. Nucleic Acids Res 1995, 23:4092-4096.
6. Breaker RR: DNA enzymes. Nat Biotech 1997, 15:427-431.
7. Jaeger L: The new world of ribozymes. Curr Opin Struct Biol 1997, 7:324-335.
8. Breaker RR: DNA aptamers and DNA enzymes. Curr Opin Chem Biol 1997, 1:26-31
9. Benner SA, Ellington AP, Tauer A: Modern metabolism as a palimpsest of the RNA world. Proc Natl Acad Sci USA 1989, 86:7654-7656.
10. Gilbert W: The RNA world. Nature 1986, 319:618.
11. Yarus M: How many catalytic RNAs? Ions and the Cheshire cat conjecture. FASEB J 1993, 7:31-39.
12. Pyle AM: Ribozymes: a distinct class of metalloenzymes. Science 1993, 261:709-714.
13. Prudent JR, Uno T, Schultz PG: Expanding the scope of RNA catalysis. Science 1994, 264:1924-1927.
14. Conn MM, Prudent JR, Schultz PG: Porphyrin metallation catalyzed by a small RNA molecule. J Am Chem Soc 1996, 118:7012-7013.
15. Schultz PG, Lerner RA: From molecular diversity to catalysis: lessons from the immune system. Science 1995, 269:1835-1842.
16. Li Y, Sen D: Towards an efficient DNAzyme. Biochemistry 1997, 36:5589-5599. A small, guanine-rich oligomer, PS5.ST1, had been reported to be an enzyme involved in the metallation of porphyrins by copper and zinc ions. This paper reports a detailed study of the properties of this enzyme, and of their optimization. It is shown, for instance, that this DNAzyme does not bind the copper ions necessary for metallation. The optimized catalytic properties of this DNAzyme compare surprisingly well with those of a catalytic antibody for the same reaction.
17. Li Y, Sen D: The modus operandi of a DNA enzyme: enhancement of substrate basicity. Chem Biol 1998, 5:1-12. This paper reports an investigation of the mode of catalytic action of the porplyrin-metallating DNAzyme, PS5.M. UV - visible absorption and fluorescence measurements revealed that the spectra of the substrate - DNAzyme complex more closely resembled those of the transition-state analog for this reaction, rather than to the spectra of the substrate itself. Further experiments revealed that the DNAzyme raised the protonation pK for the substrate mesoporphyrin IX by between 3 and 4 pH units. This paper reported the first detailed investigation of the catalytic strategy of a DNAzyme, allowing for comparisons to be made with the respective strategies used by RNA and protein enzymes for the same reaction.
18. Cochran AG, Schultz PG: Antibody-catalyzed porphyrin metallation. Science 1990, 249:781-783.
19. Travascio P, Li Y, Sen D: DNA-enhanced peroxidase activity of a DNA aptamer-hemin complex. Chem Biol 1998, 5:505-517. Two porphyrin-binding DNA aptamers, PS5.M and PS2.M, which were shown to be enzymes involved in porphyrin metallation, showed quite different enzymatic activities when complexed to hemin, a competitive inhibitor of the metallation reaction. The hemin - DNA complexes exhibited peroxidase activity two orders of magnitude higher than that of hemin itself. This was the first example of a ribozyme or DNAzyme with explicit redox activity.
20. Roth A, Breaker RR: An amino acid as a cofactor for a catalytic polynucleotide. Proc Natl Acad Sci USA 1998, 95:6027-6031. A tour-de-force of in vitro selection provided a RNA phosphodiester bond cleaving DNA enzyme that required L-histidine as an essential cofactor. Although the amino acid did not bind strongly to the DNAzyme, it was required stringently. Neither D-histidine nor dipeptides containing L-histidine functioned as cofactors. The imidazole moiety within the histidine was proposed to act as a general base for activating the 2' hydroxyl nucleophile; however, it remains to be shown whether the amino acid plays a direct role in the chemistry, as opposed to playing a role in determining the active structure of this DNAzyme.
21. Geyer CR, Sen D: Lanthanide probes for a phosphodiester-cleaving, lead-dependent, DNAzyme. J Mol Biol 1998, 275:483-489. Lanthanides are useful probes for studying metal ion interactions in biological systems. This paper describes that lanthanide ions were able to function as effective cofactors for a previously defined, lead-dependent, phosphodiester-cleaving DNA enzyme [1]. Luminescence spectroscopy with a bound terbium cofactor revealed that the 2' hydroxyl group at the cleavage site was critical for lanthanide ion binding, and that the substrate DNA/RNA molecule alone contributed substantially to determining the catalytically relevant metal-binding site. This paper reported data contrary to a widely-held notion that general base catalysis of lead-cofactor-bound hydroxides was critical for lead-dependent RNA cleavage.
22. Bunzli J-CG, Hoppin GR (Eds): Chemical and Earth Sciences. New York: Elsevier; 1989.
23. Karraker DG: Coordination of trivalent lanthanide ions. J Chem Educ 1970, 47:424-430.
24. Topal MD, Fresco JR: Fluorescence of terbium ion-nucleic acid complexes: a sensitive specific probe for unpaired residues in nucleic acids. Biochemistry 1980, 19:5531-5537.
25. 3+ bound to tRNA. Biophys Chem 1985, 21:91-101.
26. Klakamp SL, Horrocks WD: Lanthanide ion luminescence as a probe of DNA structure. 1. Guanine-containing oligomers and nucleotides. J Inorg Biochem 1992, 46:175-192.
27. Brown RS, Hingerty BE, Dewan JC, Klug A: Pb(II)-catalyzed cleavage of the sugar-phosphate backbone of yeast tRNAphe - implications for lead toxicity and self-splicing RNA. Nature 1983, 303:543-546.
28. 8-fold catalysis can be achieved by this DNAzyme. In other words, although ribozymes are sometimes regarded generically to be metalloenzymes, the purely nucleic acid components of ribozymes and DNAzymes may play substantial roles in the overall catalysis.
29. ••].
30. 2+ ion as a cofactor for a novel RNA-cleaving deoxyribozyme. Angew Chem Int Ed Engl 1996, 35:2837-2841.
31. Santoro SW, Joyce GF: A general-purpose RNA-cleaving DNA enzyme. Proc Natl Acad. Sci. USA 1997, 94:4262-4266. An excellent paper showing off the practical side of DNAzymes. A general and very high efficiency DNAzyme was described for the cleavage of extended stretches of RNA of essentially any sequence. As a test case, HIV-1 genomic RNA was neutralized effectively in vitro by DNAzymes of this class targeted against it.
32. Burmeister J, von Kiedrowski G, Ellington AD: Cofactor-assisted self-cleavage in DNA libraries with a 3'-5' phosphoramidate bond. Angew Chem Int Ed Engl 1997, 36:1321-1324. A DNAzyme is described that hydrolyzed an internal phosphoramidate linkage in the presence of a small oligonucleotide cofactor.
33. Carmi N, Schultz LA, Breaker RR: In vitro selection of self-cleaving DNAs. Chem Biol 1996, 3:1039-1046.
34. Carmi N, Balkhi SR, Breaker RR: Cleaving DNA with DNA. Proc Natl Acad Sci USA 1998, 95:2233-2237. This paper followed up from Carmi et al. [33] in defining the minimal enzymatic core of the copper-mediated self cleaving DNA molecules. It further reported on the creation of a system for catalyzing DNA-cleavage in trans. 'Restriction enzyme'-like DNAzyme motifs were generated, which were able to cleave an assortment of single-stranded target sequences via the formation of specific enzyme-substrate complexes built with duplex- and triplex-based recognition domains.
35. Dugas H: Bioorganic Chemistry: a Chemical Approach to Enzyme Action. New York: Springer Verlag; 1996.
36. Herschlag D: RNA chaperones and the RNA folding problem. J Biol Chem 1995, 270:20871-20874.
37. Barbier B, Brack A: Conformation-controlled hydrolysis of polyribonucleotides by sequential basic polypeptides. J Am Chem Soc 1992, 114:3511-3515.
38. Tung C, Wei Z, Leibowitz MJ, Stein S: Design of peptide-acridine mimics of ribonuclease activity. Proc Natl Acad Sci USA 1996, 89:7114-7118.
39. Sheehan JC, BennettGB, Schneider JA: Synthetic peptide models of enzyme active sites. III. Stereoselective esterase models. J Am Chem Soc 1966, 88:3455-3456.
40. Komiyama M, Inokawa T: Selective hydrolysis of tRNA by ethylenediamine bound to a DNA oligomer. J Biochem 1994, 116:719-720.
41. Endo M, Hirata K, Ihara T, Sueda S, Takagi M, Komiyama M: RNA hydrolysis by the cooperation of carboxylate anion and ammonium ion. J Am Chem Soc 1996, 118:5478-5479.
42. Vlassov VV, Zuber G, Felden B, Behr J, Giege R: Cleavage of tRNA with imidazole and spermine imidazole constructs: a new approach for probing RNA structure. Nucleic Acids Res 1995, 23:3161-3167.
43. Behmoroas T, Toulme J, Helene C: Specific recognition of apurinic sites in DNA by a tryptophan-containing peptide. Proc Natl Acad Sci USA 1981, 78:926-930.
44. Mayer R, Toulme J, Helene C: The role of tyrosine in the association of proteins and nucleic acids. J Biol Chem 1979, 254:75-82.
45. Brun F, Toulme J, Helene C: Interactions of aromatic residues or protein with nucleic acids. Fluorescence sutdies of the binding of oligopeptides containing tryptophan and tyrosine residues to polynucleotides. Biochemistry 1975, 14:558-563.
46. Connell JG, YarusM: RNAs with dual specificity and dual RNAs with similar specificity. Science 1994, 264:1137-1141.
47. 13C NMR. J Am Chem Soc 1994, 116:8390-8391.
48. Legault P, Pardi A: Unusual dynamics and pKa shift at the active site of a lead-dependent ribozyme. J Am Chem Soc 1997, 119:6621-6628.
49. Bruice TC: Some pertinent aspects of mechanism as determined with small molecules. Annu Rev Biochem 1970, 45:331-373.
50. Williamson JR: G-quartet structures in telomeric DNA. Annu Rev Biophys Biomol Struct 1994, 23:703-730.
51. Wellinger RJ, Sen D: The DNA structures at the ends of eukaryotic chromosomes. Eur J Cancer 1997, 33:735-749.
52. Tang J, Breaker RR: Design of allosteric ribozymes. Chem Biol 1997, 4:453-459.