Skip to main content
SpringerLink
Log in

An Integrated Picture of HDV Ribozyme Catalysis

  • Chapter
  • First Online:
Biophysics of RNA Folding

Part of the book series: Biophysics for the Life Sciences ((BIOPHYS,volume 3))

Abstract

The hepatitis delta virus (HDV) ribozyme, a small self-cleaving RNA originally identified in the human pathogen HDV, has been found to be broadly dispersed throughout life. In this article, we describe an integrated approach to understand the catalytic mechanism of this ribozyme that combines kinetics, crystallography, Raman spectroscopy, and calculations. Kinetics studies provide rate and binding parameters for protons and metal ions, and allow for design of properly folded and catalytically relevant RNAs for crystallography. Raman studies on these crystals provide direct evidence that the nucleobase of C75 has a shifted pK a. Moreover, Raman crystallography and solution kinetics demonstrate that proton binding to the N3 of C75 couples anticooperatively with binding of a Mg2+ ion, suggesting that the two species are close in space. Extensive structural studies on this ribozyme suggest that the cleavage reaction proceeds through a combination of Lewis acid catalysis by a catalytic Mg2+ ion and general acid catalysis by the nucleobase of C75. Molecular dynamics and electrostatics calculations support the above mechanism and reveal an intensely electronegative pocket that plays key roles in positioning the catalytic metal ion and C75 for catalysis. Integrating the results of kinetics, X-ray crystallography, Raman crystallography, and molecular dynamics suggests that there is a second Mg2+ ion in the active site that is bound diffusely and may play a structural role. In sum, these four disparate approaches provide for a robust kinetic mechanism for the HDV ribozyme that lays groundwork for future studies into its detailed mechanism of dynamics and cleavage.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams PL, Stahley MR, Kosek AB, Wang J, Strobel SA (2004) Crystal structure of a self-splicing group I intron with both exons. Nature 430(6995):45–50

    Article  PubMed  CAS  Google Scholar 

  • Basolo R, Person R (1988) Mechanisms of inorganic reactions. Wiley, New York

    Google Scholar 

  • Brown TS, Chadalavada DM, Bevilacqua PC (2004) Design of a highly reactive HDV ribozyme sequence uncovers facilitation of RNA folding by alternative pairings and physiological ionic strength. J Mol Biol 341(3):695–712. doi:10.1016/j.jmb.2004.05.071

    Article  PubMed  CAS  Google Scholar 

  • Carey PR (1982) Biochemical applications of raman and resonance raman spectroscopies. Academic, New York

    Google Scholar 

  • Carey PR (2006) Raman crystallography and other biochemical applications of raman microscopy. Ann Rev Phys Chem 57:527–554

    Article  CAS  Google Scholar 

  • Cerrone-Szakal AL, Chadalavada DM, Golden BL, Bevilacqua PC (2008) Mechanistic characterization of the HDV genomic ribozyme: the cleavage site base pair plays a structural role in facilitating catalysis. RNA 14(9):1746–1760. doi:10.1261/rna.1140308

    Article  PubMed  CAS  Google Scholar 

  • Chadalavada DM, Cerrone-Szakal AL, Bevilacqua PC (2007) Wild-type is the optimal sequence of the HDV ribozyme under cotranscriptional conditions. RNA 13(12):2189–2201. doi:10.1261/rna.778107

    Article  PubMed  CAS  Google Scholar 

  • Chadalavada DM, Gratton EA, Bevilacqua PC (2010) The human HDV-like CPEB3 ribozyme is intrinsically fast-reacting. Biochemistry 49(25):5321–5330. doi:10.1021/bi100434c

    Article  PubMed  CAS  Google Scholar 

  • Chadalavada DM, Knudsen SM, Nakano S, Bevilacqua PC (2000) A role for upstream RNA structure in facilitating the catalytic fold of the genomic hepatitis delta virus ribozyme. J Mol Biol 301(2):349–367. doi:10.1006/jmbi.2000.3953

    Article  PubMed  CAS  Google Scholar 

  • Chadalavada DM, Senchak SE, Bevilacqua PC (2002) The folding pathway of the genomic hepatitis delta virus ribozyme is dominated by slow folding of the pseudoknots. J Mol Biol 317(4):559–575. doi:10.1006/jmbi.2002.5434

    Article  PubMed  CAS  Google Scholar 

  • Chen JH, Gong B, Bevilacqua PC, Carey PR, Golden BL (2009) A catalytic metal ion interacts with the cleavage Site G.U wobble in the HDV ribozyme. Biochemistry 48(7):1498–1507. doi:10.1021/bi8020108

    Article  PubMed  CAS  Google Scholar 

  • Chen JH, Yajima R, Chadalavada DM, Chase E, Bevilacqua PC, Golden BL (2010) A 1.9 A crystal structure of the HDV ribozyme precleavage suggests both Lewis acid and general acid mechanisms contribute to phosphodiester cleavage. Biochemistry 49(31):6508–6518. doi:10.1021/bi100670p

    Article  PubMed  CAS  Google Scholar 

  • Christian EL, Anderson VE, Carey PR, Harris ME (2010) A quantitative Raman spectroscopic signal for metal-phosphodiester interactions in solution. Biochemistry 49(13):2869–2879. doi:10.1021/bi901866u

    Article  PubMed  CAS  Google Scholar 

  • Cochrane JC, Lipchock SV, Strobel SA (2007) Structural investigation of the GlmS ribozyme bound to Its catalytic cofactor. Chem Biol 14(1):97–105. doi:10.1016/j.chembiol.2006.12.005

    Article  PubMed  CAS  Google Scholar 

  • Curtis EA, Bartel DP (2001) The hammerhead cleavage reaction in monovalent cations. RNA 7(4):546–552

    Article  PubMed  CAS  Google Scholar 

  • Das SR, Piccirilli JA (2005) General acid catalysis by the hepatitis delta virus ribozyme. Nat Chem Biol 1(1):45–52. doi:10.1038/nchembio703

    Article  PubMed  CAS  Google Scholar 

  • DeRose VJ (2003) Metal ion binding to catalytic RNA molecules. Curr Opin Struct Biol 13(3):317–324

    Article  PubMed  CAS  Google Scholar 

  • Draper DE (2004) A guide to ions and RNA structure. RNA 10(3):335–343

    Article  PubMed  CAS  Google Scholar 

  • Duguid J, Bloomfield VA, Benevides J, Thomas GJ Jr (1993) Raman spectroscopy of DNA-metal complexes. I. Interactions and conformational effects of the divalent cations: Mg, Ca, Sr, Ba, Mn, Co, Ni, Cu, Pd, and Cd. Biophys J 65(5):1916–1928. doi:10.1016/S0006-3495(93)81263-3

    Article  PubMed  CAS  Google Scholar 

  • Eickbush DG, Eickbush TH (2010) R2 retrotransposons encode a self-cleaving ribozyme for processing from an rRNA cotranscript. Mol Cell Biol 30(13):3142–3150. doi:10.1128/MCB.00300-10

    Article  PubMed  CAS  Google Scholar 

  • Emilsson GM, Nakamura S, Roth A, Breaker RR (2003) Ribozyme speed limits. RNA 9(8):907–918

    Article  PubMed  CAS  Google Scholar 

  • Fauzi H, Kawakami J, Nishikawa F, Nishikawa S (1997) Analysis of the cleavage reaction of a trans-acting human hepatitis delta virus ribozyme. Nucleic Acids Res 25(15):3124–3130

    Article  PubMed  CAS  Google Scholar 

  • Fedor MJ (2009) Comparative enzymology and structural biology of RNA self-cleavage. Annu Rev Biophys 38:271–299. doi:10.1146/annurev.biophys.050708.133710

    Article  PubMed  CAS  Google Scholar 

  • Feig AL, Uhlenbeck OC (1999) The role of metal ions in RNA biochemistry. In: Gestlend R, Cech T, Atkins J (eds) The RNA World, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harber, NY, pp 287–319

    Google Scholar 

  • Ferre-D’Amare AR (2011) Use of a coenzyme by the glmS ribozyme-riboswitch suggests primordial expansion of RNA chemistry by small molecules. Philos Trans R Soc Lond B Biol Sci 366(1580):2942–2948. doi:10.1098/rstb.2011.0131

    Article  PubMed  Google Scholar 

  • Ferre-D’Amare AR, Doudna JA (2000) Crystallization and structure determination of a hepatitis delta virus ribozyme: Use of the RNA-binding protein U1A as a crystallization module. J Mol Biol 295(3):541–556

    Article  PubMed  Google Scholar 

  • Ferre-D’Amare AR, Zhou KH, Doudna JA (1998) Crystal structure of a hepatitis delta virus ribozyme. Nature 395(6702):567–574

    Article  PubMed  Google Scholar 

  • Frederiksen JK, Piccirilli JA (2009) Identification of catalytic metal ion ligands in ribozymes. Methods 49(2):148–166. doi:10.1016/j.ymeth.2009.07.005

    Article  PubMed  CAS  Google Scholar 

  • Ganguly A, Bevilacqua PC, Hammes-Schiffer S (2011) Quantum Mechanical/Molecular Mechanical Study of the HDV Ribozyme: Impact of the Catalytic Metal Ion on the Mechanism. J Phys Chem Lett 2(22):2906–2911. doi:10.1021/jz2013215

    Article  PubMed  CAS  Google Scholar 

  • Golden BL (2011) Two distince catalytic strategies in the HDV ribozyme cleavage reaction. Biochemistry 50(44):9424–9433

    Article  PubMed  CAS  Google Scholar 

  • Golden BL, Kim H, Chase E (2005) Crystal structure of a phage twort group I ribozyme-product complex. Nat Struct Mol Biol 12(1):82–89

    Article  PubMed  CAS  Google Scholar 

  • Gong B, Chen JH, Bevilacqua PC, Golden BL, Carey PR (2009a) Competition between Co(NH(3)(6)3+ and inner sphere Mg2+ ions in the HDV ribozyme. Biochemistry 48(50):11961–11970. doi:10.1021/bi901091v

    Article  PubMed  CAS  Google Scholar 

  • Gong B, Chen JH, Chase E, Chadalavada DM, Yajima R, Golden BL, Bevilacqua PC, Carey PR (2007) Direct measurement of a pK(a) near neutrality for the catalytic cytosine in the genomic HDV ribozyme using Raman crystallography. J Am Chem Soc 129(43):13335–13342. doi:10.1021/ja0743893

    Article  PubMed  CAS  Google Scholar 

  • Gong B, Chen JH, Yajima R, Chen Y, Chase E, Chadalavada DM, Golden BL, Carey PR, Bevilacqua PC (2009b) Raman crystallography of RNA. Methods 49(2):101–111. doi:10.1016/j.ymeth.2009.04.016

    Article  PubMed  CAS  Google Scholar 

  • Gong B, Chen Y, Christian EL, Chen JH, Chase E, Chadalavada DM, Yajima R, Golden BL, Bevilacqua PC, Carey PR (2008) Detection of innersphere interactions between magnesium hydrate and the phosphate backbone of the HDV ribozyme using Raman crystallography. J Am Chem Soc 130(30):9670–9672. doi:10.1021/ja801861s

    Article  PubMed  CAS  Google Scholar 

  • Gong B, Klein DJ, Ferre-D’Amare AR, Carey PR (2011) The glmS Ribozyme Tunes the Catalytically Critical pK(a) of Its Coenzyme Glucosamine-6-phosphate. J Am Chem Soc 133(36):14188–14191. doi:10.1021/ja205185g

    Article  PubMed  CAS  Google Scholar 

  • Guerrier-Takada C, Gardiner K, Marsh T, Pace N, Altman S (1983) The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35(3 Pt 2):849–857

    Article  PubMed  CAS  Google Scholar 

  • Guo F, Gooding A, Cech TR (2004) Structure of the tetrahymena ribozyme: Base triple sandwhich and metal ion at the active site. Mol Cell 16(3):351–362

    PubMed  CAS  Google Scholar 

  • Guo M, Spitale RC, Volpini R, Krucinska J, Cristalli G, Carey PR, Wedekind JE (2009) Direct Raman measurement of an elevated base pKa in the active site of a small ribozyme in a precatalytic conformation. J Am Chem Soc 131(36):12908–12909. doi:10.1021/ja9060883

    Article  PubMed  CAS  Google Scholar 

  • Harris DA, Tinsley RA, Walter NG (2004) Terbium-mediated footprinting probes a catalytic conformational switch in the antigenomic hepatitis delta virus ribozyme. J Mol Biol 341(2):389–403. doi:10.1016/j.jmb.2004.05.074

    Article  PubMed  CAS  Google Scholar 

  • Isambert H, Siggia ED (2000) Modeling RNA folding paths with pseudoknots: application to hepatitis delta virus ribozyme. Proc Natl Acad Sci USA 97(12):6515–6520. doi:10.1073/pnas.110533697

    Article  PubMed  CAS  Google Scholar 

  • Jou R, Cowan J (1991) Ribonuclease H activation by inert transition-metal complexes. Mechanistic probes for metallocofactors: insights on the metallobiochemistry of divalent magnesium ion J Am Chem Soc 113:6685–6686

    CAS  Google Scholar 

  • Ke A, Zhou K, Ding F, Cate JH, Doudna JA (2004) A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature 429(6988):201–205

    Article  PubMed  CAS  Google Scholar 

  • Klein DJ, Been MD, Ferre-D’Amare AR (2007) Essential role of an active-site guanine in glmS ribozyme catalysis. J Am Chem Soc 129(48):14858–14859. doi:10.1021/ja0768441

    Article  PubMed  CAS  Google Scholar 

  • Klein DJ, Ferre-D’Amare AR (2006) Structural basis of glmS ribozyme activation by glucosamine-6-phosphate. Science 313(5794):1752–1756. doi:10.1126/science.1129666

    Article  PubMed  CAS  Google Scholar 

  • Krasovska MV, Sefcikova J, Spackova N, Sponer J, Walter NG (2005) Structural dynamics of precursor and product of the RNA enzyme from the hepatitis delta virus as revealed by molecular dynamics simulations. J Mol Biol 351(4):731–748. doi:10.1016/j.jmb.2005.06.016

    Article  PubMed  CAS  Google Scholar 

  • Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR (1982) Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31(1):147–157

    Article  PubMed  CAS  Google Scholar 

  • Kuo MY, Sharmeen L, Dinter-Gottlieb G, Taylor J (1988) Characterization of self-cleaving RNA sequences on the genome and antigenome of human hepatitis delta virus. J Virol 62(12):4439–4444

    PubMed  CAS  Google Scholar 

  • Long DA (2002) The Raman effect. John Wiley & Sons, Ltd. doi:10.1002/0470845767

    Google Scholar 

  • Luptak A, Ferre-D’Amare AR, Zhou K, Zilm KW, Doudna JA (2001) Direct pK(a) measurement of the active-site cytosine in a genomic hepatitis delta virus ribozyme. J Am Chem Soc 123(35):8447–8452

    Article  PubMed  CAS  Google Scholar 

  • Mansy .S, Chu G.Y-H, Ducan RE, Tobias RS (1978). Heavy metal-nucleotide interactions. 12. Competitive reactions in systems of far nudeotides with cis- and trans-diamine platinum (II). Raman difference spectrophatometric determination of the relative nucleophilicity of guanine, cytidine, adenosine and uridine monophosphates as well as the analogous bases in DNA. J Am Chen Soc 100(2): 607–616.

    Article  PubMed  CAS  Google Scholar 

  • Martick M, Scott WG (2006) Tertiary contacts distant from the active site prime a ribozyme for catalysis. Cell 126(2):309–320. doi:10.1016/j.cell.2006.06.036

    Article  PubMed  CAS  Google Scholar 

  • Moller MR, Bruck MA, O’Connor T, Armatis FJ, Edward A Jr (1980) Heavy metal-nucleotide interactions. 14. Raman difference spectrophometric studies of competitive reactions in mixtures of four nucleotides with electrophiles. Factors governing selectivity in the binding reaction. J Am Chem Soc 102(14):4589–4598

    Article  CAS  Google Scholar 

  • Nakano S, Bevilacqua PC (2007) Mechanistic characterization of the HDV genomic ribozyme: a mutant of the C41 motif provides insight into the positioning and thermodynamic linkage of metal ions and protons. Biochemistry 46(11):3001–3012. doi:10.1021/bi061732s

    Article  PubMed  CAS  Google Scholar 

  • Nakano S, Cerrone AL, Bevilacqua PC (2003) Mechanistic characterization of the HDV genomic ribozyme: classifying the catalytic and structural metal ion sites within a multichannel reaction mechanism. Biochemistry 42(10):2982–2994. doi:10.1021/bi026815x

    Article  PubMed  CAS  Google Scholar 

  • Nakano S, Chadalavada DM, Bevilacqua PC (2000) General acid–base catalysis in the mechanism of a hepatitis delta virus ribozyme. Science 287(5457):1493–1497

    Article  PubMed  CAS  Google Scholar 

  • Nakano S, Proctor DJ, Bevilacqua PC (2001) Mechanistic characterization of the HDV genomic ribozyme: assessing the catalytic and structural contributions of divalent metal ions within a multichannel reaction mechanism. Biochemistry 40(40):12022–12038

    Article  PubMed  CAS  Google Scholar 

  • O’Rear JL, Wang S, Feig AL, Beigelman L, Uhlenbeck OC, Herschlag D (2001) Comparison of the hammerhead cleavage reactions stimulated by monovalent and divalent cations. RNA 7(4):537–545

    Article  PubMed  Google Scholar 

  • Oyelere AK, Kardon JR, Strobel SA (2002) pK(a) perturbation in genomic Hepatitis Delta Virus ribozyme catalysis evidenced by nucleotide analogue interference mapping. Biochemistry 41(11):3667–3675

    Article  PubMed  CAS  Google Scholar 

  • Peleg M (1972) A Raman spectroscopic investigation of the magesnium nitrate-water system. J Phys Chem 76:1019–1025

    Article  CAS  Google Scholar 

  • Pereira MJ, Harris DA, Rueda D, Walter NG (2002) Reaction pathway of the trans-acting hepatitis delta virus ribozyme: a conformational change accompanies catalysis. Biochemistry 41(3):730–740

    Article  PubMed  CAS  Google Scholar 

  • Perrotta AT, Been MD (1991) A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA. Nature 350(6317):434–436. doi:10.1038/350434a0

    Article  PubMed  CAS  Google Scholar 

  • Perrotta AT, Shih I, Been MD (1999) Imidazole rescue of a cytosine mutation in a self-cleaving ribozyme. Science 286(5437):123–126

    Article  PubMed  CAS  Google Scholar 

  • Perrotta AT, Wadkins TS, Been MD (2006) Chemical rescue, multiple ionizable groups, and general acid–base catalysis in the HDV genomic ribozyme. RNA 12(7):1282–1291. doi:10.1261/rna.14106

    Article  PubMed  CAS  Google Scholar 

  • Pye CC, Rudolph WW (1998) An ab initio and Raman investigation of magnesium(II) hydration. J Phys Chem A 102(48):9933–9943

    Article  CAS  Google Scholar 

  • Reid CE, Lazinski DW (2000) A host-specific function is required for ligation of a wide variety of ribozyme-processed RNAs. Proc Natl Acad Sci USA 97(1):424–429

    Article  PubMed  CAS  Google Scholar 

  • Reiter NJ, Osterman A, Torres-Larios A, Swinger KK, Pan T, Mondragon A (2010) Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA. Nature 468(7325):784–789. doi:10.1038/nature09516

    Article  PubMed  CAS  Google Scholar 

  • Rosenstein SP, Been MD (1990) Self-cleavage of hepatitis delta virus genomic strand RNA is enhanced under partially denaturing conditions. Biochemistry 29(35):8011–8016

    Article  PubMed  CAS  Google Scholar 

  • Rupert PB, Ferre-D’Amare AR (2001) Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis. Nature 410(6830):780–786

    Article  PubMed  CAS  Google Scholar 

  • Salehi-Ashtiani K, Luptak A, Litovchick A, Szostak JW (2006) A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science 313(5794):1788–1792. doi:10.1126/science.1129308

    Article  PubMed  CAS  Google Scholar 

  • Salehi-Ashtiani K, Szostak JW (2001) In vitro evolution suggests multiple origins for the hammerhead ribozyme. Nature 414(6859):82–84. doi:10.1038/35102081

    Article  PubMed  CAS  Google Scholar 

  • Savochkina L, Alekseenkova V, Belyanko T, Dobrynina N, Beabealashvilli R (2008) RNase ­footprinting demonstrates antigenomic hepatitis delta virus ribozyme structural rearrangement as a result of self-cleavage reaction. BMC Res Notes 1:15. doi:10.1186/1756-0500-1-15

    Article  PubMed  Google Scholar 

  • Sharmeen L, Kuo MY, Dinter-Gottlieb G, Taylor J (1988) Antigenomic RNA of human hepatitis delta virus can undergo self-cleavage. J Virol 62(8):2674–2679

    PubMed  CAS  Google Scholar 

  • Shih IH, Been MD (2001a) Energetic contribution of non-essential 5′ sequence to catalysis in a hepatitis delta virus ribozyme. EMBO J 20(17):4884–4891. doi:10.1093/emboj/20.17.4884

    Article  CAS  Google Scholar 

  • Shih IH, Been MD (2001b) Involvement of a cytosine side chain in proton transfer in the ­rate-determining step of ribozyme self-cleavage. Proc Natl Acad Sci USA 98(4):1489–1494. doi:10.1073/pnas.98.4.1489

    Article  PubMed  CAS  Google Scholar 

  • Smith JB, Dinter-Gottlieb G (1991) Antigenomic Hepatitis delta virus ribozymes self-cleave in 18 M formamide. Nucleic Acids Res 19(6):1285–1289

    Article  PubMed  CAS  Google Scholar 

  • Steitz TA, Steitz JA (1993) A general two-metal-ion mechanism for catalytic RNA. Proc Natl Acad Sci USA 90(14):6498–6502

    Article  PubMed  CAS  Google Scholar 

  • Suga H, Cowan JA, Szostak JW (1998) Unusual metal ion catalysis in an acyl-transferase ribozyme. Biochemistry 37(28):10118–10125. doi:10.1021/bi980432a

    Article  PubMed  CAS  Google Scholar 

  • Thomas GJ, Tsuboi M (1993) Laser Raman spectroscopy of nucleic acids. Adv Biophys Chem 3:1–70

    CAS  Google Scholar 

  • Tinsley RA, Harris DA, Walter NG (2004) Magnesium dependence of the amplified conformational switch in the trans-acting hepatitis delta virus ribozyme. Biochemistry 43(28):8935–8945. doi:10.1021/bi049471e

    Article  PubMed  CAS  Google Scholar 

  • Toor N, Keating KS, Taylor SD, Pyle AM (2008) Crystal structure of a self-spliced group II intron. Science 320(5872):77–82. doi:10.1126/science.1153803

    Article  PubMed  CAS  Google Scholar 

  • Veeraraghavan N, Bevilacqua PC, Hammes-Schiffer S (2010) Long-distance communication in the HDV ribozyme: insights from molecular dynamics and experiments. J Mol Biol 402(1):278–291. doi:10.1016/j.jmb.2010.07.025

    Article  PubMed  CAS  Google Scholar 

  • Veeraraghavan N, Ganguly A, Chen JH, Bevilacqua PC, Hammes-Schiffer S, Golden BL (2011a) Metal binding motif in the active site of the HDV ribozyme binds divalent and monovalent ions. Biochemistry 50(13):2672–2682. doi:10.1021/bi2000164

    Article  PubMed  CAS  Google Scholar 

  • Veeraraghavan N, Ganguly A, Golden BL, Bevilacqua PC, Hammes-Schiffer S (2011b) Mechanistic Strategies in the HDV Ribozyme: Chelated and Diffuse Metal Ion Interactions and Active Site Protonation. J Phys Chem B. doi:10.1021/jp203202e

  • Vogler C, Spalek K, Aerni A, Demougin P, Muller A, Huynh KD, Papassotiropoulos A, de Quervain DJ (2009) CPEB3 is associated with human episodic memory. Front Behav Neurosci 3:4. doi:10.3389/neuro.08.004.2009

    Article  PubMed  Google Scholar 

  • Wadkins TS, Been MD (2002) Ribozyme activity in the genomic and antigenomic RNA strands of hepatitis delta virus. Cellular and molecular life sciences: CMLS 59(1):112–125

    Article  PubMed  CAS  Google Scholar 

  • Wadkins TS, Perrotta AT, Ferre-D’Amare AR, Doudna JA, Been MD (1999) A nested double pseudoknot is required for self-cleavage activity of both the genomic and antigenomic hepatitis delta virus ribozymes. RNA 5(6):720–727

    Article  PubMed  CAS  Google Scholar 

  • Wadkins TS, Shih I, Perrotta AT, Been MD (2001) A pH-sensitive RNA tertiary interaction affects self-cleavage activity of the HDV ribozymes in the absence of added divalent metal ion. J Mol Biol 305(5):1045–1055. doi:10.1006/jmbi.2000.4368

    Article  PubMed  CAS  Google Scholar 

  • Webb CH, Luptak A (2011) HDV-like self-cleaving ribozymes. RNA Biol 8(5)

    Google Scholar 

  • Webb CH, Riccitelli NJ, Ruminski DJ, Luptak A (2009) Widespread occurrence of self-cleaving ribozymes Science 326(5955):953. doi:10.1126/science.1178084

    CAS  Google Scholar 

  • Wilson DS, Szostak JW (1999) In vitro selection of functional nucleic acids. Annu Rev Biochem 68:611–647. doi:10.1146/annurev.biochem.68.1.611

    Article  PubMed  CAS  Google Scholar 

  • Wu HN, Lin YJ, Lin FP, Makino S, Chang MF, Lai MM (1989) Human hepatitis delta virus RNA subfragments contain an autocleavage activity. Proc Natl Acad Sci USA 86(6):1831–1835

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge Peter Breen, Trevor Brown, Andrea Cerrone-Szakal, Durga Chadalavada, Elaine Chase, J. Chen, Jui-Hui Chen, Yuanyuan Chen, Eric Christian, Abir Ganguly, Bo Gong, Shu-ichi Nakano, Pallavi Thaplyal, Narayanan Veeraraghavan, and Rieko Yajima for their contributions to this project. These studies were supported by GM095923 (to BLG and PCB), GM81420 (to PRC), and GM56207 (to SHS).

Author information

Authors and Affiliations

  1. Department of Biochemistry, Purdue University, 175 South University Street, West Lafayette, IN, 47907, USA

    Barbara L. Golden

  2. Department of Chemistry, The Pennsylvania State University, 104 Chemistry Building, University Park, PA, 16802, USA

    Sharon Hammes-Schiffer & Philip C. Bevilacqua

  3. Department of Biochemistry, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106, USA

    Paul R. Carey

Authors
  1. Barbara L. Golden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharon Hammes-Schiffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul R. Carey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philip C. Bevilacqua
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barbara L. Golden .

Editor information

Editors and Affiliations

  1. , Dept. of Chemistry and Biochemistry, University of Texas, Austin, 78712, Texas, USA

    Rick Russell

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Golden, B.L., Hammes-Schiffer, S., Carey, P.R., Bevilacqua, P.C. (2013). An Integrated Picture of HDV Ribozyme Catalysis. In: Russell, R. (eds) Biophysics of RNA Folding. Biophysics for the Life Sciences, vol 3. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4954-6_8

Download citation

Publish with us

Policies and ethics

Search

Navigation