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A comparison of vanadate to a 2'-5' linkage at the active site of a small ribozyme suggests a role for water in transition-state stabilization.

Torelli AT, Krucinska J, Wedekind JE
RNA 13 1052-70 (2007)
Related entries: 1x9c, 1x9k, 1zft, 1zfv, 1zfx, 2bcy, 2bcz, 2d2k, 2d2l, 2fgp, 2oue, 2p7d, 2p7f

Cited: 38 times
EuropePMC logo PMID: 17488874

Abstract

The potential for water to participate in RNA catalyzed reactions has been the topic of several recent studies. Here, we report crystals of a minimal, hinged hairpin ribozyme in complex with the transition-state analog vanadate at 2.05 A resolution. Waters are present in the active site and are discussed in light of existing views of catalytic strategies employed by the hairpin ribozyme. A second structure harboring a 2',5'-phosphodiester linkage at the site of cleavage was also solved at 2.35 A resolution and corroborates the assignment of active site waters in the structure containing vanadate. A comparison of the two structures reveals that the 2',5' structure adopts a conformation that resembles the reaction intermediate in terms of (1) the positioning of its nonbridging oxygens and (2) the covalent attachment of the 2'-O nucleophile with the scissile G+1 phosphorus. The 2',5'-linked structure was then overlaid with scissile bonds of other small ribozymes including the glmS metabolite-sensing riboswitch and the hammerhead ribozyme, and suggests the potential of the 2',5' linkage to elicit a reaction-intermediate conformation without the need to form metalloenzyme complexes. The hairpin ribozyme structures presented here also suggest how water molecules bound at each of the nonbridging oxygens of G+1 may electrostatically stabilize the transition state in a manner that supplements nucleobase functional groups. Such coordination has not been reported for small ribozymes, but is consistent with the structures of protein enzymes. Overall, this work establishes significant parallels between the RNA and protein enzyme worlds.

Articles - 2p7e mentioned but not cited (6)

  1. A comparison of vanadate to a 2'-5' linkage at the active site of a small ribozyme suggests a role for water in transition-state stabilization. Torelli AT, Krucinska J, Wedekind JE. RNA 13 1052-1070 (2007)
  2. Molecular dynamics suggest multifunctionality of an adenine imino group in acid-base catalysis of the hairpin ribozyme. Ditzler MA, Sponer J, Walter NG. RNA 15 560-575 (2009)
  3. Evidence for the role of active site residues in the hairpin ribozyme from molecular simulations along the reaction path. Heldenbrand H, Janowski PA, Giambaşu G, Giese TJ, Wedekind JE, York DM. J Am Chem Soc 136 7789-7792 (2014)
  4. Shared traits on the reaction coordinates of ribonuclease and an RNA enzyme. Torelli AT, Spitale RC, Krucinska J, Wedekind JE. Biochem Biophys Res Commun 371 154-158 (2008)
  5. Mutational inhibition of ligation in the hairpin ribozyme: substitutions of conserved nucleobases A9 and A10 destabilize tertiary structure and selectively promote cleavage. Gaur S, Heckman JE, Burke JM. RNA 14 55-65 (2008)
  6. Determination of an effective scoring function for RNA-RNA interactions with a physics-based double-iterative method. Yan Y, Wen Z, Zhang D, Huang SY. Nucleic Acids Res 46 e56 (2018)


Reviews citing this publication (8)

  1. Comparative enzymology and structural biology of RNA self-cleavage. Fedor MJ. Annu Rev Biophys 38 271-299 (2009)
  2. Theoretical studies of RNA catalysis: hybrid QM/MM methods and their comparison with MD and QM. Banás P, Jurecka P, Walter NG, Sponer J, Otyepka M. Methods 49 202-216 (2009)
  3. Ribozyme catalysis revisited: is water involved? Walter NG. Mol Cell 28 923-929 (2007)
  4. Focus on function: single molecule RNA enzymology. Ditzler MA, Alemán EA, Rueda D, Walter NG. Biopolymers 87 302-316 (2007)
  5. The glmS ribozyme: use of a small molecule coenzyme by a gene-regulatory RNA. Ferré-D'Amaré AR. Q Rev Biophys 43 423-447 (2010)
  6. Two distinct catalytic strategies in the hepatitis δ virus ribozyme cleavage reaction. Golden BL. Biochemistry 50 9424-9433 (2011)
  7. Base ionization and ligand binding: how small ribozymes and riboswitches gain a foothold in a protein world. Liberman JA, Wedekind JE. Curr Opin Struct Biol 21 327-334 (2011)
  8. Exploring ribozyme conformational changes with X-ray crystallography. Spitale RC, Wedekind JE. Methods 49 87-100 (2009)

Articles citing this publication (24)

  1. Classification and energetics of the base-phosphate interactions in RNA. Zirbel CL, Sponer JE, Sponer J, Stombaugh J, Leontis NB. Nucleic Acids Res 37 4898-4918 (2009)
  2. Quantum mechanical/molecular mechanical simulation study of the mechanism of hairpin ribozyme catalysis. Nam K, Gao J, York DM. J Am Chem Soc 130 4680-4691 (2008)
  3. Extensive molecular dynamics simulations showing that canonical G8 and protonated A38H+ forms are most consistent with crystal structures of hairpin ribozyme. Mlýnský V, Banás P, Hollas D, Réblová K, Walter NG, Sponer J, Otyepka M. J Phys Chem B 114 6642-6652 (2010)
  4. Multistrand RNA secondary structure prediction and nanostructure design including pseudoknots. Bindewald E, Afonin K, Jaeger L, Shapiro BA. ACS Nano 5 9542-9551 (2011)
  5. Direct Raman measurement of an elevated base pKa in the active site of a small ribozyme in a precatalytic conformation. Guo M, Spitale RC, Volpini R, Krucinska J, Cristalli G, Carey PR, Wedekind JE. J Am Chem Soc 131 12908-12909 (2009)
  6. Direct measurement of the ionization state of an essential guanine in the hairpin ribozyme. Liu L, Cottrell JW, Scott LG, Fedor MJ. Nat Chem Biol 5 351-357 (2009)
  7. Electrostatic interactions in the hairpin ribozyme account for the majority of the rate acceleration without chemical participation by nucleobases. Nam K, Gao J, York DM. RNA 14 1501-1507 (2008)
  8. The pH dependence of hairpin ribozyme catalysis reflects ionization of an active site adenine. Cottrell JW, Scott LG, Fedor MJ. J Biol Chem 286 17658-17664 (2011)
  9. Structural effects of nucleobase variations at key active site residue Ade38 in the hairpin ribozyme. MacElrevey C, Salter JD, Krucinska J, Wedekind JE. RNA 14 1600-1616 (2008)
  10. Identification of an imino group indispensable for cleavage by a small ribozyme. Spitale RC, Volpini R, Heller MG, Krucinska J, Cristalli G, Wedekind JE. J Am Chem Soc 131 6093-6095 (2009)
  11. QM/MM studies of hairpin ribozyme self-cleavage suggest the feasibility of multiple competing reaction mechanisms. Mlýnský V, Banáš P, Walter NG, Šponer J, Otyepka M. J Phys Chem B 115 13911-13924 (2011)
  12. Catalytic importance of a protonated adenosine in the hairpin ribozyme active site. Suydam IT, Levandoski SD, Strobel SA. Biochemistry 49 3723-3732 (2010)
  13. Noncanonical hydrogen bonding in nucleic acids. Benchmark evaluation of key base-phosphate interactions in folded RNA molecules using quantum-chemical calculations and molecular dynamics simulations. Zgarbová M, Jurečka P, Banáš P, Otyepka M, Sponer JE, Leontis NB, Zirbel CL, Sponer J. J Phys Chem A 115 11277-11292 (2011)
  14. A transition-state interaction shifts nucleobase ionization toward neutrality to facilitate small ribozyme catalysis. Liberman JA, Guo M, Jenkins JL, Krucinska J, Chen Y, Carey PR, Wedekind JE. J Am Chem Soc 134 16933-16936 (2012)
  15. Crucial Roles of Two Hydrated Mg2+ Ions in Reaction Catalysis of the Pistol Ribozyme. Teplova M, Falschlunger C, Krasheninina O, Egger M, Ren A, Patel DJ, Micura R. Angew Chem Int Ed Engl 59 2837-2843 (2020)
  16. Crystallographic analysis of small ribozymes and riboswitches. Lippa GM, Liberman JA, Jenkins JL, Krucinska J, Salim M, Wedekind JE. Methods Mol Biol 848 159-184 (2012)
  17. Design of hairpin ribozyme variants with improved activity for poorly processed substrates. Drude I, Strahl A, Galla D, Müller O, Müller S. FEBS J 278 622-633 (2011)
  18. Strand-specific (asymmetric) contribution of phosphodiester linkages on RNA polymerase II transcriptional efficiency and fidelity. Xu L, Zhang L, Chong J, Xu J, Huang X, Wang D. Proc Natl Acad Sci U S A 111 E3269-76 (2014)
  19. Single-atom imino substitutions at A9 and A10 reveal distinct effects on the fold and function of the hairpin ribozyme catalytic core. Spitale RC, Volpini R, Mungillo MV, Krucinska J, Cristalli G, Wedekind JE. Biochemistry 48 7777-7779 (2009)
  20. Multiscale methods for computational RNA enzymology. Panteva MT, Dissanayake T, Chen H, Radak BK, Kuechler ER, Giambaşu GM, Lee TS, York DM. Methods Enzymol 553 335-374 (2015)
  21. The Small Ribozymes: Common and Diverse Features Observed through the FRET Lens. Walter NG, Perumal S. Springer Ser Biophys 13 103-127 (2009)
  22. Intermolecular domain docking in the hairpin ribozyme: metal dependence, binding kinetics and catalysis. Sumita M, White NA, Julien KR, Hoogstraten CG. RNA Biol 10 425-435 (2013)
  23. Investigation of the pKa of the Nucleophilic O2' of the Hairpin Ribozyme. Veenis AJ, Li P, Soudackov AV, Hammes-Schiffer S, Bevilacqua PC. J Phys Chem B 125 11869-11883 (2021)
  24. RR3DD: an RNA global structure-based RNA three-dimensional structural classification database. Hong X, Zheng J, Xie J, Tong X, Liu X, Song Q, Liu S, Liu S. RNA Biol 18 738-746 (2021)


Related citations provided by authors (2)

  1. Water in the active site of an all-RNA hairpin ribozyme and effects of Gua8 base variants on the geometry of phosphoryl transfer.. Salter J, Krucinska J, Alam S, Grum-Tokars V, Wedekind JE Biochemistry 45 686-700 (2006)
  2. Conformational heterogeneity at position U37 of an all-RNA hairpin ribozyme with implications for metal binding and the catalytic structure of the S-turn.. Alam S, Grum-Tokars V, Krucinska J, Kundracik ML, Wedekind JE Biochemistry 44 14396-408 (2005)

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