Deoxyribozymes: New players in the ancient game of biocatalysis

Current Opinion in Structural Biology

Volumn 9, Issue 3, 1999, Pages 315-323

  Li, Yingfu ^a   Breaker, Ronald R ^a  

^a YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; DEOXYRIBOZYME; DNA; ENZYME; METAL ION; PEROXIDASE; PORPHYRIN; RIBOZYME; RNA; UNCLASSIFIED DRUG;

CATALYSIS; DNA CLEAVAGE; DNA STRUCTURE; ENZYME ACTIVITY; PRIORITY JOURNAL; REVIEW; RNA CLEAVAGE;

EID: 0033150946     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-440X(99)80042-6     Document Type: Article

References (61)

1. Breaker RR: DNA enzymes. Nat Biotechnol 1997, 15:427-431. This essay compares the chemical and structural features of protein, RNA and DNA, providing an assessment of the catalytic potential of DNA and its implications for biocatalysis.
2. Williams KP, Bartel DP: In vitro selection of catalytic RNA. Nucleic Acids Mol Biol 1996, 98:961-990.
3. Lorsch JR, Szostak JW: Chances and necessity in the selection of nucleic acid catalysis. Accounts Chem Res 1996, 29:103-110.
4. Breaker RR: In vitro selection of catalytic polynucleotides. Chem Rev 1997, 97:371-390.
5. Burgstaller P, Famulok M: Synthetic ribozymes and the first deoxyribozyme. Angew Chem Int Ed Engl 1995, 34:1189-1192.
6. Breaker RR: DNA aptamers and DNA enzymes. Curr Opin Chem Biol 1997, 1:26-31.
7. Sen D, Geyer CR: DNA enzymes. Curr Opin Chem Biol 1998, 2:680-687.
8. Breaker RR, Joyce GF: A DNA enzyme that cleaves RNA. Chem Biol 1994, 1:223-229.
9. 2+-dependent RNA phosphoesterase activity. Chem Biol 1995, 2:655-660.
10. Cuenoud B, Szostak JW: A DNA metalloenzyme with ligase activity. Nature 1995, 375:611-614.
11. Li Y, Sen D: A catalytic DNA for porphyrin metallation. Nat Struct Biol 1996, 3:743-747.
12. 2+ ion as a cofactor for a novel RNA cleaving deoxyribozyme. Angew Chem Int Ed Engl 1996, 35:2837-2841.
13. Faulhammer D, Famulok M: Characterization and divalent metal-ion dependence of in vitro selected deoxyribozymes which cleave DNA/RNA chimeric oligonucleotides. J Mol Biol 1997, 269:188-202.
14. Geyer CR, Sen D: Lanthanide probes for a phosphodiester-cleaving, lead- dependent, DNAzyme. J Mol Biol 1998, 275:483-489.
15. Yarus M: How many catalytic RNAs? Ions and the Cheshire cat conjecture. FASEB J 1993, 7:31-39.
16. Pyle AM: Ribozymes: A distinct class of metalloenzymes. Science 1993, 261:709-714.
17. Hampel A, Cowan JA: A unique mechanism for RNA catalysis: The role of metal cofactors in hairpin ribozyme cleavage. Chem Biol 1997, 4:513-517.
18. Nesbitt S, Hegg LA, Fedor MJ: An unusual pH-independent and metal-ion-independent mechanism for hairpin ribozyme catalysis. Chem Biol 1997, 4:619-630.
19. Young KJ, Gill F, Grasby JA: Metal ions play a passive role in the hairpin ribozyme catalysed reaction. Nucleic Acids Res 1997, 25:3760-3766.
20. Murray JB, Seyhan AA, Walter NG. Burke JM, Scott WG: The hammerhead, hairpin and VS ribozymes are catalytically proficient in monovalent cations alone. Chem Biol 1998, 5:587-595.
21. Suga H, Cowan JA, Szostak JW: Unusual metal ion catalysis in an acyltransferase ribozyme. Biochemistry 1998, 37:10118-10125.
22. Geyer CR, Sen D: Evidence for the metal-cofactor independence of an RNA phosphodiester-cleaving DNA enzyme. Chem Biol 1997, 4:579-593. This report describes the isolation and characterization of an RNA-cleaving deoxyribozyme that does not require a divalent metal ion as a cofactor. Although definitively ruling out the participation of minute traces of divalent cations is difficult, this point has been rigorously investigated and convincingly demonstrated by the authors. The novel deoxyribozyme is capable of providing a rate enhancement for RNA transesterification that rivals that of metal-dependent ribozymes, suggesting that DNA has a significant intrinsic ability to catalyze RNA-cleavage reactions.
23. Roth A, Breaker RR: An amino acid as a cofactor for a catalytic polynucleotide. Proc Natl Acad Sci USA 1998, 95:6027-6031. Four new classes of RNA-cleaving deoxyribozymes are described in this report. Three classes are active in the absence of added divalent metals, whereas the remaining deoxyribozyme requires the amino acid histidine for catalytic function. The latter deoxyribozyme promotes RNA transesterification in the presence of L-histidine with a rate enhancement of approximately one-million-fold over the uncatalyzed reaction. This finding demonstrates that amino acids and other cofactors can be used by nucleic acid enzymes to augment their otherwise limited chemical repertoire. Moreover, the histidine-dependent deoxyribozyme strongly discriminates against D-histidine and a variety of histidine analogs, indicating that DNA is also capable of performing precise molecular recognition.
24. Narlikar GJ, Herschlag D: Mechanistic aspects of enzymatic catalysis: Lessons from comparison of RNA and protein enzymes. Annu Rev Biochem 1997, 66:19-59. A comprehensive and insightful discussion relating to the catalytic mechanisms of protein and nucleic acid enzymes. Many of the concepts presented in this review pertain to the catalytic potential of DNA.
25. Tarasow TM, Tarasow SL, Eaton BE: RNA-catalysed carbon-carbon bond formation. Nature 1997, 389:54-57.
26. Wiegand TW, Janssen RC, Eaton BE: Selection of RNA amide synthases. Chem Biol 1997, 4:675-683.
27. Eaton BE: The joys of in vitro selection: Chemically dressing oligonucleotides to satiate protein targets. Curr Opin Chem Biol 1997, 1:10-16.
28. Sakthivel K, Barbas CF III: Expanding the potential of DNA for binding and catalysis: Highly functionalized dUTP derivatives that are substrates for thermostable DNA polymerases. Angew Chem Int Ed Engl 1998, 37:2872-2875. The authors established a chemical system whereby diverse combinations of functional groups can be introduced into DNA. With the incorporation of additional chemical modifications, the structural and functional diversity are sure to be enhanced.
29. Walsh C: In Enzymatic Reaction Mechanisms. New York: WH Freeman; 1979:202-207.
30. Santoro SW, Joyce GF: A general-purpose RNA-cleaving DNA enzyme. Proc Natl Acad Sci USA 1997, 94:4262-4266. A small, but highly efficient deoxyribozyme was isolated that can be engineered to cleave pyrimidine-purine junctions in almost any RNA sequence. The catalytic core of the deoxyribozyme consists of only 15 nucleotides, flanked by two sequence domains that bind the RNA substrate through Watson-Crick base pairing (see Figure 2). The 10-23 deoxyribozyme is a promising candidate for development as a designer endoribonuclease for both in vitro and in vivo applications.
31. Santoro SW, Joyce GF: Mechanism and utility of an RNA-cleaving DNA enzyme. Biochemistry 1998, 37:13330-13342. The authors provide a detailed kinetic examination of the 10-23 deoxyribozyme. This work establishes a foundation for its possible utilization as a highly specific RNA-cleaving deoxyribozyme.
32. Nowakowski J, Shim PJ, Prasad GS, Stout CD, Joyce GF: Crystal structure of an 82-nucleotide RNA-DNA complex formed by the 10-23 DNA enzyme. Nat Struct Biol 1999, 6:151-156. The authors describe the atomic resolution structure of the largest DNA complex reported to date. Unfortunately, the Holliday-junction-like complex, formed by two RNA substrates and two deoxyribozymes, does not reflect the active structure of the 10-23 deoxyribozyme. The model does, however, provide a glimpse of the level of structural complexity that can be achieved by DNA.
33. Ota N, Warashina M, Hirano K, Hatanaka K, Taira K: Effects of helical structures formed by the binding arms of DNAzymes and their substrates on catalytic activity. Nucleic Acids Res 1998, 26:3385-3391.
34. 2+ on complex formation between a deoxyribozyme and its substrates. Nucleosides Nucleotides 1998, 17:565-574.
35. Li Y, Sen D: Towards an efficient DNAzyme. Biochemistry 1997, 36:5589-5599. A detailed kinetic analysis of catalysis by a porphyrin-metalating DNA enzyme is given. In addition, a direct comparison of the enzymatic parameters for the corresponding protein and RNA enzymes is made, revealing that the three enzyme formats provide similar catalytic rate enhancements.
36. Sugimoto N, Toda T, Ohmichi T: Reaction field for efficient porphyrin metallation catalysis by self-assembly of a short DNA oligonucleotide. Chem Commun 1998:1533-1534.
37. Li Y, Geyer CR, Sen D: Recognition of anionic porphyrins by DNA aptamers. Biochemistry 1996, 35:6911-6922.
38. Cochran AG, Schultz PG: Antibody-catalysed porphyrin metallation. Science 1990, 249:781-783.
39. Conn MM, Prudent JR, Schultz PG: Porphyrin metalation catalyzed by a small RNA molecule. J Am Chem Soc 1996, 118:7012-7013.
40. Li Y, Sen D: The modus operandi of a DNA enzyme: Enhancement of substrate basicity. Chem Biol 1998, 5:1-12. The complex formed between a porphyrin-metalating deoxyribozyme and a planar porphyrin substrate was investigated using spectroscopic methods. The deoxyribozyme-bound porphyrin substrate exhibits a UV visible absorption pattern that is different from that of free substrate porphyrin, but, instead, resembles that of the distorted porphyrin used to derive the original DNA aptamer. It was further revealed that the deoxyribozyme increases the basicity of the bound porphyrin substrate by 3-4 pH units in order to ease the metalation reaction.
41. Travascio P, Li Y, Sen D: DNA-enhanced peroxidase activity of a DNA aptamer-hemin complex. Chem Biol 1998, 5:505-517. Similar to the porphyrin-metalating catalytic antibody [38], the PS2.M deoxyribozyme has dual catalytic activity for porphyrin metalation and heminassisted peroxidation. Although modest in catalytic rate enhancement, the findings demonstrate that similar catalytic functions could be achieved by nucleic acid enzymes.
42. Carmi N, Shultz LA, Breaker RR: In vitro selection of self-cleaving DNAs. Chem Biol 1996, 3:1039-1046.
43. 2+-dependent deoxyribozyme. This class II self-cleaving DNA can be engineered to perform like an artificial restriction enzyme and can be made to cleave single-stranded DNAs of a defined sequence. Interestingly, the deoxyribozyme uses both duplex and triplex DNA structures to recognize and position DNA target sequences.
44. Frank-Kamenetskii MD, Mirkin SM: Triplex DNA structures. Annu Rev Biochem 1995, 64:65-95.
45. Sun J, Garestier T, Helénè C: Oligonucleotide directed triple helix formation. Curr Opin Struct Biol 1996, 6:327-333.
46. Wolfenden R, Ridgway C, Young G: Spontaneous hydrolysis of ionized phosphate monoesters and diesters and the proficiencies of phosphatases and phosphodiesterases as catalysts. J Am Chem Soc 1998, 120:833-834.
47. 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.
48. Li Y, Breaker RR: Phosphorylating DNA with DNA. Proc Natl Acad Sci USA 1999, 96:2746-2751. This manuscript showcases DNA's capacity for structure formation, catalysis and molecular recognition. Nearly 50 distinct classes of deoxyribozymes have been created that catalyze self-phosphorylation with distinct requirements for the form of NTP or dNTP used as the source of activated phosphate. An individual ATP-dependent deoxyribozyme can be engineered to phosphorylate separate DNA substrates of defined sequence.
49. Lorsch JR, Szostak JW: In vitro evolution of new ribozymes with polynucleotide kinase activity. Nature 1994, 371:31-36.
50. Lillehaug JR, Kleppe K: Kinetics and specificity of T4 polynucleotide kinase. Biochemistry 1975, 14:1221-1225.
51. Fedor MJ, Uhlenbeck OC: Kinetics of intermolecular cleavage by hammerhead ribozyme. Biochemistry 1992, 31:12042-12054.
52. Hampel A, Tritz R: RNA catalytic properties of the minimum (-) sTRSV sequence. Biochemistry 1992, 28:4929-4933.
53. DelCardayre SB, Raines RT: Structural determinants of enzymatic processivity. Biochemistry 1994, 33:6031-6037.
54. Williamson JR: Guanine quartets. Curr Opin Struct Biol 1993, 3:357-362.
55. Pyle AM, Green JB: RNA folding. Curr Opin Struct Biol 1995, 5:303-310.
56. Cate JH, Goodling AR, Podell E, Zhou K, Golden BL, Kundrot CE, Cech TR, Doudna JA: Crystal structure of a group I ribozyme domain: Principles of RNA packing. Science 1996, 273:1678-1685.
57. Wang S, Chen J, Yu K, Li M, Li L: Deoxyribozyme (I) - Esterase activity of DNA in Phaseolus aureus. Acta Sci Nat Univ Norm Hunan 1995, 18:59-62.
58. Sabeti PC, Unrau PJ, Bartel DP: Accessing rare activities from random RNA sequences: The importance of the length of molecules in the starting pool. Chem Biol 1997, 4:767-774.
59. Soukup GA, Breaker RR: Engineering precision RNA molecular switches. Proc Natl Acad Sci USA 1999, 96:3584-3589.
60. Warashina M, Kuwabara T, Nakamatsu Y, Taira K: Extremely high and specific activity of DNA enzymes in cells with Philadelphia chromosome. Chem Biol 1999, 6:237-250.
61. Cairns TH, Witherington C, Wang L, Sun L-Q: Target site selection for RNA-cleaving catalytic DNA. Nat Biotechnol 1999, 17:480-486.