Ribozyme catalysis: not different, just worse

Evolution has resoundingly favored protein enzymes over RNA-based catalysts, yet ribozymes occupy important niches in modern cell biology that include the starring role in catalysis of protein synthesis on the ribosome. Recent results from structural and biochemical studies show that natural ribozymes use an impressive range of catalytic mechanisms, beyond metalloenzyme chemistry and analogous to more chemically diverse protein enzymes. These findings make it increasingly possible to compare details of RNA- and protein-based catalysis.

[1]  T. Steitz,et al.  The structural basis of ribosome activity in peptide bond synthesis. , 2000, Science.

[2]  E. Westhof,et al.  Sequence elements outside the hammerhead ribozyme catalytic core enable intracellular activity , 2003, Nature Structural Biology.

[3]  R. Raines.  Active Site of Ribonuclease A , 2004 .

[4]  Anastasia Khvorova,et al.  Fast cleavage kinetics of a natural hammerhead ribozyme. , 2004, Journal of the American Chemical Society.

[5]  M. Fedor,et al.  An unusual pH-independent and metal-ion-independent mechanism for hairpin ribozyme catalysis. , 1997, Chemistry & biology.

[6]  R R Breaker,et al.  Structural diversity of self-cleaving ribozymes. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Doudna,et al.  Stereochemical course of catalysis by the Tetrahymena ribozyme. , 1989, Science.

[8]  J. Doudna,et al.  Structural Insights into Group II Intron Catalysis and Branch-Site Selection , 2002, Science.

[9]  John M. Burke,et al.  A conformational change in the "loop E-like" motif of the hairpin ribozyme is coincidental with domain docking and is essential for catalysis. , 2001, Biochemistry.

[10]  W. Jencks.  Catalysis in chemistry and enzymology , 1969 .

[11]  V. Sklená,et al.  Formation of a stable triplex from a single DNA strand , 1990, Nature.

[12]  W. Scott,et al.  Does a single metal ion bridge the A-9 and scissile phosphate groups in the catalytically active hammerhead ribozyme structure? , 2000, Journal of molecular biology.

[13]  M. Fedor,et al.  Role of an active site guanine in hairpin ribozyme catalysis probed by exogenous nucleobase rescue. , 2004, Journal of molecular biology.

[14]  W. Scott,et al.  Capture and visualization of a catalytic RNA enzyme-product complex using crystal lattice trapping and X-ray holographic reconstruction. , 2000, Molecular cell.

[15]  S. Nakano,et al.  Mechanistic characterization of the HDV genomic ribozyme: assessing the catalytic and structural contributions of divalent metal ions within a multichannel reaction mechanism. , 2001, Biochemistry.

[16]  R. Breaker,et al.  Control of gene expression by a natural metabolite-responsive ribozyme , 2004, Nature.

[17]  A. Fersht,et al.  Catalysis, binding and enzyme-substrate complementarity , 1974, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[18]  T. Cech,et al.  Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 2. Kinetic description of the reaction of an RNA substrate that forms a mismatch at the active site. , 1990, Biochemistry.

[19]  C. Kundrot,et al.  Crystal Structure of a Group I Ribozyme Domain: Principles of RNA Packing , 1996, Science.

[20]  Rachel Green,et al.  The Active Site of the Ribosome Is Composed of Two Layers of Conserved Nucleotides with Distinct Roles in Peptide Bond Formation and Peptide Release , 2004, Cell.

[21]  T. Cech,et al.  Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 1. Kinetic description of the reaction of an RNA substrate complementary to the active site. , 1990, Biochemistry.

[22]  P. Bevilacqua.  Mechanistic considerations for general acid-base catalysis by RNA: revisiting the mechanism of the hairpin ribozyme. , 2003, Biochemistry.

[23]  E Westhof,et al.  New loop-loop tertiary interactions in self-splicing introns of subgroup IC and ID: a complete 3D model of the Tetrahymena thermophila ribozyme. , 1996, Chemistry & biology.

[24]  Wolfgang Wintermeyer,et al.  Important contribution to catalysis of peptide bond formation by a single ionizing group within the ribosome. , 2002, Molecular cell.

[25]  John M. Burke,et al.  Solvent protection of the hammerhead ribozyme in the ground state: evidence for a cation-assisted conformational change leading to catalysis. , 2003, Biochemistry.

[26]  D. Herschlag,et al.  Mechanistic aspects of enzymatic catalysis: lessons from comparison of RNA and protein enzymes. , 1997, Annual review of biochemistry.

[27]  I. Shih,et al.  Imidazole rescue of a cytosine mutation in a self-cleaving ribozyme. , 1999, Science.

[28]  O. Uhlenbeck,et al.  Comparison of the hammerhead cleavage reactions stimulated by monovalent and divalent cations. , 2001, RNA.

[29]  D. Herschlag,et al.  Use of binding energy by an RNA enzyme for catalysis by positioning and substrate destabilization. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. S. Weinger,et al.  Substrate-assisted catalysis of peptide bond formation by the ribosome , 2004, Nature Structural &Molecular Biology.

[31]  S. Pedersen.  Escherichia coli ribosomes translate in vivo with variable rate. , 1984, The EMBO journal.

[32]  J. Scott,et al.  A place in the world for RNA editing , 1995, Cell.

[33]  A. W. Hanson,et al.  The three-dimensional structure of ribonuclease-S. Interpretation of an electron density map at a nominal resolution of 2 A. , 1970, The Journal of biological chemistry.

[34]  W. Scott,et al.  The Structural Basis of Hammerhead Ribozyme Self-Cleavage , 1998, Cell.

[35]  J. Steitz,et al.  A general two-metal-ion mechanism for catalytic RNA. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[36]  J. Cowan,et al.  A unique mechanism for RNA catalysis: the role of metal cofactors in hairpin ribozyme cleavage. , 1997, Chemistry & biology.

[37]  R. Raines,et al.  Energetics of catalysis by ribonucleases: fate of the 2',3'-cyclic phosphodiester intermediate. , 1994, Biochemistry.

[38]  Daniel Herschlag,et al.  Probing the role of metal ions in RNA catalysis: kinetic and thermodynamic characterization of a metal ion interaction with the 2'-moiety of the guanosine nucleophile in the Tetrahymena group I ribozyme. , 1999, Biochemistry.

[39]  O. Uhlenbeck,et al.  A re-investigation of the thio effect at the hammerhead cleavage site. , 1999, Nucleic acids research.

[40]  C. Condon,et al.  Construction and Initial Characterization of Escherichia coli Strains with Few or No Intact Chromosomal rRNA Operons , 1999, Journal of bacteriology.

[41]  D. Herschlag,et al.  Defining the catalytic metal ion interactions in the Tetrahymena ribozyme reaction. , 2001, Biochemistry.

[42]  A. Bohm,et al.  Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin , 2002, Nature.

[43]  E. Westhof,et al.  A three‐dimensional perspective on exon binding by a group II self‐splicing intron , 2000, The EMBO journal.

[44]  H. Noller,et al.  A base pair between tRNA and 23S rRNA in the peptidyl transferase centre of the ribosome , 1995, Nature.

[45]  H. Noller,et al.  Mutations at nucleotides G2251 and U2585 of 23 S rRNA perturb the peptidyl transferase center of the ribosome. , 1997, Journal of molecular biology.

[46]  D. Herschlag,et al.  Three metal ions at the active site of the Tetrahymena group I ribozyme. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[47]  S. Strobel,et al.  Investigation of adenosine base ionization in the hairpin ribozyme by nucleotide analog interference mapping. , 2001, RNA.

[48]  A. Murray.  MAP Kinases in Meiosis , 1998, Cell.

[49]  M. J. Pereira,et al.  Reaction pathway of the trans-acting hepatitis delta virus ribozyme: a conformational change accompanies catalysis. , 2002, Biochemistry.

[50]  Jennifer A. Doudna,et al.  A conformational switch controls hepatitis delta virus ribozyme catalysis , 2004, Nature.

[51]  H. Noller,et al.  Unusual resistance of peptidyl transferase to protein extraction procedures. , 1992, Science.

[52]  O. Uhlenbeck,et al.  Thiophosphate interference experiments locate phosphates important for the hammerhead RNA self-cleavage reaction. , 1990, Nucleic acids research.

[53]  L. J. Su,et al.  Visualizing the solvent‐inaccessible core of a group II intron ribozyme , 2001, The EMBO journal.

[54]  A. Ferré-D’Amaré,et al.  Direct pK(a) measurement of the active-site cytosine in a genomic hepatitis delta virus ribozyme. , 2001, Journal of the American Chemical Society.

[55]  M. Marahiel,et al.  Learning from Nature's Drug Factories: Nonribosomal Synthesisof MacrocyclicPeptides , 2003, Journal of bacteriology.

[56]  W. Scott,et al.  The hammerhead, hairpin and VS ribozymes are catalytically proficient in monovalent cations alone. , 1998, Chemistry & biology.

[57]  W. Scott,et al.  A pH-dependent conformational change, rather than the chemical step, appears to be rate-limiting in the hammerhead ribozyme cleavage reaction. , 2002, Journal of molecular biology.

[58]  S. Nakano,et al.  General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme. , 2000, Science.

[59]  B. Golden,et al.  Crystal structure of a phage Twort group I ribozyme–product complex , 2005, Nature Structural &Molecular Biology.

[60]  J. Feigon,et al.  Adenine protonation in domain B of the hairpin ribozyme. , 2000, Biochemistry.

[61]  Christopher T Walsh,et al.  Polyketide and Nonribosomal Peptide Antibiotics: Modularity and Versatility , 2004, Science.

[62]  D. Lilley,et al.  Observation of internal cleavage and ligation reactions of a ribozyme , 2004, Nature Structural &Molecular Biology.

[63]  T. Cech,et al.  A preorganized active site in the crystal structure of the Tetrahymena ribozyme. , 1998, Science.

[64]  L. Amzel,et al.  Role of entropy in increased rates of intramolecular reactions. , 2003, Journal of the American Chemical Society.

[65]  Tan Inoue,et al.  Modular engineering of a Group I intron ribozyme. , 2002, Nucleic acids research.

[66]  T. Steitz,et al.  The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. , 2000, Science.

[67]  A. Klug,et al.  The crystal structure of an AII-RNAhammerhead ribozyme: A proposed mechanism for RNA catalytic cleavage , 1995, Cell.

[68]  D. Lilley,et al.  Folding of the natural hammerhead ribozyme is enhanced by interaction of auxiliary elements. , 2004, RNA.

[69]  D. Herschlag,et al.  Identification of the hammerhead ribozyme metal ion binding site responsible for rescue of the deleterious effect of a cleavage site phosphorothioate. , 1999, Biochemistry.

[70]  B. Stoddard,et al.  Capturing the Structure of a Catalytic RNA Intermediate: The Hammerhead Ribozyme , 1996, Science.

[71]  W. Scott,et al.  A helical twist-induced conformational switch activates cleavage in the hammerhead ribozyme. , 2003, Journal of molecular biology.

[72]  T. Steitz,et al.  A pre-translocational intermediate in protein synthesis observed in crystals of enzymatically active 50S subunits , 2002, Nature Structural Biology.

[73]  Scott A. Strobel,et al.  Crystal structure of a self-splicing group I intron with both exons , 2004, Nature.

[74]  S. Strobel,et al.  A single adenosine with a neutral pKa in the ribosomal peptidyl transferase center. , 2000, Science.

[75]  Annette Sievers,et al.  The ribosome as an entropy trap. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[76]  J. Feigon,et al.  Triple-strand formation in the homopurine:homopyrimidine DNA oligonucleotides d(G-A)4 and d(T-C)4 , 1989, Nature.

[77]  G. S. Wickham,et al.  Self-cleaving ribozymes of hepatitis delta virus RNA. , 1997, European journal of biochemistry.

[78]  T. Cech,et al.  Stereochemistry of RNA cleavage by the Tetrahymena ribozyme and evidence that the chemical step is not rate-limiting. , 1989, Science.

[79]  A. Ferré-D’Amaré,et al.  Transition State Stabilization by a Catalytic RNA , 2002, Science.

[80]  T. Cech,et al.  Structure of the Tetrahymena ribozyme: base triple sandwich and metal ion at the active site. , 2004, Molecular cell.

[81]  O. Uhlenbeck,et al.  Steric interference modification of the hammerhead ribozyme. , 2002, Chemistry & biology.

[82]  Y. Zhao,et al.  Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity. , 2000, Science.

[83]  M. Fedor,et al.  Rescue of an abasic hairpin ribozyme by cationic nucleobases: evidence for a novel mechanism of RNA catalysis. , 2002, Chemistry & biology.

[84]  K. Flaherty,et al.  Three-dimensional structure of a hammerhead ribozyme , 1994, Nature.

[85]  H. Noller,et al.  Ribosome-catalyzed peptide-bond formation with an A-site substrate covalently linked to 23S ribosomal RNA. , 1998, Science.

[86]  Jack W. Szostak,et al.  In vitro evolution suggests multiple origins for the hammerhead ribozyme , 2001, Nature.

[87]  M. Caruthers,et al.  Metal ion catalysis in the Tetrahymena ribozyme reaction , 1993, Nature.

[88]  A. Ferré-D’Amaré,et al.  Crystal structure of a hairpin ribozyme–inhibitor complex with implications for catalysis , 2001, Nature.

[89]  M. Massiah,et al.  Structures and mechanisms of Nudix hydrolases. , 2005, Archives of biochemistry and biophysics.

[90]  O. Uhlenbeck,et al.  Hammerhead ribozyme kinetics. , 1998, RNA.

[91]  M Yarus,et al.  RNAs with dual specificity and dual RNAs with similar specificity. , 1994, Science.

[92]  S R Sprang,et al.  Two-metal-Ion catalysis in adenylyl cyclase. , 1999, Science.

[93]  H. Noller,et al.  Interaction of tRNA with 23S rRNA in the ribosomal A, P, and E sites , 1989, Cell.

[94]  A. Ferré-D’Amaré,et al.  Crystal structure of a hepatitis delta virus ribozyme , 1998, Nature.

[95]  The P5abc peripheral element facilitates preorganization of the tetrahymena group I ribozyme for catalysis. , 2000, Biochemistry.

[96]  B. Bramlage,et al.  The hammerhead ribozyme. , 1999, Biopolymers.

[97]  J. Knowles,et al.  Enzyme catalysis: not different, just better , 1991, Nature.

[98]  N. Proudfoot,et al.  Autocatalytic RNA cleavage in the human β-globin pre-mRNA promotes transcription termination , 2004, Nature.

[99]  F. Eckstein,et al.  Phosphorothioate modification of RNA for stereochemical and interference analyses. , 2000, Methods in enzymology.

[100]  A. Pardi,et al.  In situ Probing of Adenine Protonation in RNA by 13C NMR , 1994 .

[101]  D. Bartel,et al.  The hammerhead cleavage reaction in monovalent cations. , 2001, RNA.

[102]  Ricardo Flores,et al.  Peripheral regions of natural hammerhead ribozymes greatly increase their self‐cleavage activity , 2003, The EMBO journal.

[103]  H. Ke,et al.  The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis. , 2003, Biochemistry.

[104]  Dipali G. Sashital,et al.  Solution structure of domain 5 of a group II intron ribozyme reveals a new RNA motif , 2004, Nature Structural &Molecular Biology.

[105]  O. Uhlenbeck,et al.  Involvement of a Specific Metal Ion in the Transition of the Hammerhead Ribozyme to Its Catalytic Conformation* , 1997, The Journal of Biological Chemistry.

[106]  S. Nakano,et al.  Proton inventory of the genomic HDV ribozyme in Mg(2+)-containing solutions. , 2001, Journal of the American Chemical Society.

[107]  C. Walsh,et al.  Initiation, elongation, and termination strategies in polyketide and polypeptide antibiotic biosynthesis. , 1999, Current opinion in chemical biology.

[108]  I. Shih,et al.  Involvement of a cytosine side chain in proton transfer in the rate-determining step of ribozyme self-cleavage. , 2001, Proceedings of the National Academy of Sciences of the United States of America.