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PDBsum entry 1sj3

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protein dna_rna metals links
Translation/RNA PDB id
1sj3
Jmol
Contents
Protein chain
95 a.a. *
DNA/RNA
Metals
_MG ×2
Waters ×37
* Residue conservation analysis
PDB id:
1sj3
Name: Translation/RNA
Title: Hepatitis delta virus gemonic ribozyme precursor, with mg2+
Structure: Precursor form of the hepatitis delta virus riboz chain: r. Engineered: yes. Mutation: yes. Small nuclear ribonucleoprotein a. Chain: p. Fragment: RNA binding domain. Synonym: u1 snrnp protein a. U1a protein. U1-a. Small nucle ribonucleoprotein polypeptide a.
Source: Hepatitis delta virus. Organism_taxid: 12475. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: c75u in vitro transcription. Homo sapiens. Human. Organism_taxid: 9606. Gene: snrpa.
Biol. unit: Tetramer (from PQS)
Resolution:
2.20Å     R-factor:   0.255     R-free:   0.282
Authors: A.Ke,K.Zhou,F.Ding,J.H.Cate,J.A.Doudna
Key ref:
A.Ke et al. (2004). A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature, 429, 201-205. PubMed id: 15141216 DOI: 10.1038/nature02522
Date:
02-Mar-04     Release date:   18-May-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P09012  (SNRPA_HUMAN) -  U1 small nuclear ribonucleoprotein A
Seq:
Struc:
282 a.a.
95 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     nuclear mRNA splicing, via spliceosome   1 term 
  Biochemical function     nucleotide binding     3 terms  

 

 
DOI no: 10.1038/nature02522 Nature 429:201-205 (2004)
PubMed id: 15141216  
 
 
A conformational switch controls hepatitis delta virus ribozyme catalysis.
A.Ke, K.Zhou, F.Ding, J.H.Cate, J.A.Doudna.
 
  ABSTRACT  
 
Ribozymes enhance chemical reaction rates using many of the same catalytic strategies as protein enzymes. In the hepatitis delta virus (HDV) ribozyme, site-specific self-cleavage of the viral RNA phosphodiester backbone requires both divalent cations and a cytidine nucleotide. General acid-base catalysis, substrate destabilization and global and local conformational changes have all been proposed to contribute to the ribozyme catalytic mechanism. Here we report ten crystal structures of the HDV ribozyme in its pre-cleaved state, showing that cytidine is positioned to activate the 2'-OH nucleophile in the precursor structure. This observation supports its proposed role as a general base in the reaction mechanism. Comparison of crystal structures of the ribozyme in the pre- and post-cleavage states reveals a significant conformational change in the RNA after cleavage and that a catalytically critical divalent metal ion from the active site is ejected. The HDV ribozyme has remarkable chemical similarity to protein ribonucleases and to zymogens for which conformational dynamics are integral to biological activity. This finding implies that RNA structural rearrangements control the reactivity of ribozymes and ribonucleoprotein enzymes.
 
  Selected figure(s)  
 
Figure 2.
Figure 2: Conformational changes in the active site accompany HDV ribozyme cleavage. a, 3.4 ┼ experimental electron-density map of the wild-type precursor HDV ribozyme (1 ) superimposed on the refined wild-type structure model (magenta) and that of the C75U mutant (grey). b, Backbone alignment of the precursor (magenta) and product (grey) ribozyme structures. c, Stereo view of the aligned active sites of the precursor (coloured) and product (grey) ribozyme structures. Conformational changes were modelled using the C75U mutant ribozyme structure, shown by arrows.
Figure 3.
Figure 3: Proposed mechanism for general acid -base catalysis in the HDV ribozyme. a, In the ground state, a hinge rotation along O3'-P bond brings the nucleophilic 2'-OH to the in-line attack conformation. In the transition state, C75 (the general base) deprotonates the 2'-OH whereas the bound hydrated metal ion (the general acid) protonates the 5' oxygen leaving group. Conformational changes after scissile bond breakage discharge the catalytic metal ion and down-shift the catalytic base C75 by 2 ┼ to enable hydrogen bonding with the 5'-OH of G1. b, Structural models of the HDV ribozyme in the ground state, transition state and product state. Some metal-chelating groups and coordinating waters are omitted for clarity.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2004, 429, 201-205) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22337051 E.A.Dethoff, J.Chugh, A.M.Mustoe, and H.M.Al-Hashimi (2012).
Functional complexity and regulation through RNA dynamics.
  Nature, 482, 322-330.  
21428954 D.M.Lilley (2011).
Catalysis by the nucleolytic ribozymes.
  Biochem Soc Trans, 39, 641-646.  
21857665 D.M.Shechner, and D.P.Bartel (2011).
The structural basis of RNA-catalyzed RNA polymerization.
  Nat Struct Mol Biol, 18, 1036-1042.
PDB codes: 3r1h 3r1l
21348498 N.Veeraraghavan, A.Ganguly, J.H.Chen, P.C.Bevilacqua, S.Hammes-Schiffer, and B.L.Golden (2011).
Metal binding motif in the active site of the HDV ribozyme binds divalent and monovalent ions.
  Biochemistry, 50, 2672-2682.  
20498460 C.E.Hajdin, F.Ding, N.V.Dokholyan, and K.M.Weeks (2010).
On the significance of an RNA tertiary structure prediction.
  RNA, 16, 1340-1349.  
21134640 C.Reymond, D.Lévesque, M.Bisaillon, and J.P.Perreault (2010).
Developing three-dimensional models of putative-folding intermediates of the HDV ribozyme.
  Structure, 18, 1608-1616.  
20210413 D.Jost, and R.Everaers (2010).
Prediction of RNA multiloop and pseudoknot conformations from a lattice-based, coarse-grain tertiary structure model.
  J Chem Phys, 132, 095101.  
20460458 E.Ennifar, P.Walter, and P.Dumas (2010).
Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site.
  Nucleic Acids Res, 38, 5807-5816.
PDB codes: 2oiy 2oj0
20204525 M.Giel-Pietraszuk, A.Fedoruk-Wyszomirska, and J.Barciszewski (2010).
Effect of high hydrostatic pressure on hydration and activity of ribozymes.
  Mol Biol Rep, 37, 3713-3719.  
20886091 M.J.Pereira, V.Behera, and N.G.Walter (2010).
Nondenaturing purification of co-transcriptionally folded RNA avoids common folding heterogeneity.
  PLoS One, 5, e12953.  
20547881 T.J.Wilson, N.S.Li, J.Lu, J.K.Frederiksen, J.A.Piccirilli, and D.M.Lilley (2010).
Nucleobase-mediated general acid-base catalysis in the Varkud satellite ribozyme.
  Proc Natl Acad Sci U S A, 107, 11751-11756.  
19501200 A.E.Simon, and L.Gehrke (2009).
RNA conformational changes in the life cycles of RNA viruses, viroids, and virus-associated RNAs.
  Biochim Biophys Acta, 1789, 571-583.  
18810653 A.Fedoruk-Wyszomirska, M.Giel-Pietraszuk, E.Wyszko, M.Szymański, J.Ciesiołka, M.Z.Barciszewska, and J.Barciszewski (2009).
The mechanism of acidic hydrolysis of esters explains the HDV ribozyme activity.
  Mol Biol Rep, 36, 1647-1650.  
21218180 A.R.Srinivasan, R.R.Sauers, M.O.Fenley, A.H.Boschitsch, A.Matsumoto, A.V.Colasanti, and W.K.Olson (2009).
Properties of the Nucleic-acid Bases in Free and Watson-Crick Hydrogen-bonded States: Computational Insights into the Sequence-dependent Features of Double-helical DNA.
  Biophys Rev, 1, 13-20.  
19888753 B.Gong, J.H.Chen, P.C.Bevilacqua, B.L.Golden, and P.R.Carey (2009).
Competition between Co(NH(3)(6)3+ and inner sphere Mg2+ ions in the HDV ribozyme.
  Biochemistry, 48, 11961-11970.  
19718544 C.Reymond, J.D.Beaudoin, and J.P.Perreault (2009).
Modulating RNA structure and catalysis: lessons from small cleaving ribozymes.
  Cell Mol Life Sci, 66, 3937-3950.  
19134473 C.Reymond, M.Bisaillon, and J.P.Perreault (2009).
Monitoring of an RNA multistep folding pathway by isothermal titration calorimetry.
  Biophys J, 96, 132-140.  
  20461158 Dhar, S.Ganguli, and A.Datta (2009).
Targeting pseudoknots in H5N1 hemagglutinin using designed aptamers.
  Bioinformation, 4, 193-196.  
  20160921 H.Wang, and B.M.Reinhard (2009).
Monitoring Simultaneous Distance and Orientation Changes in Discrete Dimers of DNA Linked Gold Nanoparticles.
  J Phys Chem C Nanomater Interfaces, 113, 11215-11222.  
19178151 J.H.Chen, B.Gong, P.C.Bevilacqua, P.R.Carey, and B.L.Golden (2009).
A catalytic metal ion interacts with the cleavage Site G.U wobble in the HDV ribozyme.
  Biochemistry, 48, 1498-1507.  
19864433 J.Zhang, J.Dundas, M.Lin, R.Chen, W.Wang, and J.Liang (2009).
Prediction of geometrically feasible three-dimensional structures of pseudoknotted RNA through free energy estimation.
  RNA, 15, 2248-2263.  
19223444 M.A.Ditzler, J.Sponer, and N.G.Walter (2009).
Molecular dynamics suggest multifunctionality of an adenine imino group in acid-base catalysis of the hairpin ribozyme.
  RNA, 15, 560-575.  
19416070 M.J.Fedor (2009).
Comparative enzymology and structural biology of RNA self-cleavage.
  Annu Rev Biophys, 38, 271-299.  
19398008 P.Banás, P.Jurecka, N.G.Walter, J.Sponer, and M.Otyepka (2009).
Theoretical studies of RNA catalysis: hybrid QM/MM methods and their comparison with MD and QM.
  Methods, 49, 202-216.  
19294348 Q.Wu, L.Huang, and Y.Zhang (2009).
The structure and function of catalytic RNAs.
  Sci China C Life Sci, 52, 232-244.  
18658121 A.L.Cerrone-Szakal, D.M.Chadalavada, B.L.Golden, and P.C.Bevilacqua (2008).
Mechanistic characterization of the HDV genomic ribozyme: the cleavage site base pair plays a structural role in facilitating catalysis.
  RNA, 14, 1746-1760.  
18596253 C.MacElrevey, J.D.Salter, J.Krucinska, and J.E.Wedekind (2008).
Structural effects of nucleobase variations at key active site residue Ade38 in the hairpin ribozyme.
  RNA, 14, 1600-1616.
PDB codes: 3b58 3b5a 3b5f 3b5s 3b91 3bbi 3bbk 3bbm 3cr1
18356538 D.Jaikaran, M.D.Smith, R.Mehdizadeh, J.Olive, and R.A.Collins (2008).
An important role of G638 in the cis-cleavage reaction of the Neurospora VS ribozyme revealed by a novel nucleotide analog incorporation method.
  RNA, 14, 938-949.  
18613678 J.M.Hart, S.D.Kennedy, D.H.Mathews, and D.H.Turner (2008).
NMR-assisted prediction of RNA secondary structure: identification of a probable pseudoknot in the coding region of an R2 retrotransposon.
  J Am Chem Soc, 130, 10233-10239.  
18312410 J.Wrzesinski, and S.K.Jó┼║wiakowski (2008).
Structural basis for recognition of Co2+ by RNA aptamers.
  FEBS J, 275, 1651-1662.  
17906862 J.Zhao, R.L.Malmberg, and L.Cai (2008).
Rapid ab initio prediction of RNA pseudoknots via graph tree decomposition.
  J Math Biol, 56, 145-159.  
18710542 L.Savochkina, V.Alekseenkova, T.Belyanko, N.Dobrynina, and R.Beabealashvilli (2008).
RNase footprinting demonstrates antigenomic hepatitis delta virus ribozyme structural rearrangement as a result of self-cleavage reaction.
  BMC Res Notes, 1, 15.  
18686993 P.Banás, L.Rulísek, V.Hánosová, D.Svozil, N.G.Walter, J.Sponer, and M.Otyepka (2008).
General base catalysis for cleavage by the active-site cytosine of the hepatitis delta virus ribozyme: QM/MM calculations establish chemical feasibility.
  J Phys Chem B, 112, 11177-11187.  
17355864 A.Ke, F.Ding, J.D.Batchelor, and J.A.Doudna (2007).
Structural roles of monovalent cations in the HDV ribozyme.
  Structure, 15, 281-287.
PDB codes: 2oih 2oj3
17933779 A.Nehdi, J.Perreault, J.D.Beaudoin, and J.P.Perreault (2007).
A novel structural rearrangement of hepatitis delta virus antigenomic ribozyme.
  Nucleic Acids Res, 35, 6820-6831.  
17846637 A.Serganov, and D.J.Patel (2007).
Ribozymes, riboswitches and beyond: regulation of gene expression without proteins.
  Nat Rev Genet, 8, 776-790.  
17488874 A.T.Torelli, J.Krucinska, and J.E.Wedekind (2007).
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.
  RNA, 13, 1052-1070.
PDB codes: 2p7d 2p7e 2p7f
17105991 C.Reymond, J.Ouellet, M.Bisaillon, and J.P.Perreault (2007).
Examination of the folding pathway of the antigenomic hepatitis delta virus ribozyme reveals key interactions of the L3 loop.
  RNA, 13, 44-54.  
17956974 D.M.Chadalavada, A.L.Cerrone-Szakal, and P.C.Bevilacqua (2007).
Wild-type is the optimal sequence of the HDV ribozyme under cotranscriptional conditions.
  RNA, 13, 2189-2201.  
17570822 D.M.Lilley (2007).
A chemo-genetic approach for the study of nucleobase participation in nucleolytic ribozymes.
  Biol Chem, 388, 699-704.  
17573364 E.Freyhult, V.Moulton, and P.Clote (2007).
Boltzmann probability of RNA structural neighbors and riboswitch detection.
  Bioinformatics, 23, 2054-2062.  
17337436 J.Sefcikova, M.V.Krasovska, J.Sponer, and N.G.Walter (2007).
The genomic HDV ribozyme utilizes a previously unnoticed U-turn motif to accomplish fast site-specific catalysis.
  Nucleic Acids Res, 35, 1933-1946.  
17253610 J.Sefcikova, M.V.Krasovska, N.Spacková, J.Sponer, and N.G.Walter (2007).
Impact of an extruded nucleotide on cleavage activity and dynamic catalytic core conformation of the hepatitis delta virus ribozyme.
  Biopolymers, 85, 392-406.  
18158891 N.G.Walter (2007).
Ribozyme catalysis revisited: is water involved?
  Mol Cell, 28, 923-929.  
17584608 P.M.Gordon, R.Fong, and J.A.Piccirilli (2007).
A second divalent metal ion in the group II intron reaction center.
  Chem Biol, 14, 607-612.  
17570823 R.A.Tinsley, and N.G.Walter (2007).
Long-range impact of peripheral joining elements on structure and function of the hepatitis delta virus ribozyme.
  Biol Chem, 388, 705-715.  
17666711 R.Przybilski, and C.Hammann (2007).
The tolerance to exchanges of the Watson Crick base pair in the hammerhead ribozyme core is determined by surrounding elements.
  RNA, 13, 1625-1630.  
17981494 S.A.Strobel, and J.C.Cochrane (2007).
RNA catalysis: ribozymes, ribosomes, and riboswitches.
  Curr Opin Chem Biol, 11, 636-643.  
17276459 S.Cao, and S.J.Chen (2007).
Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity.
  J Mol Biol, 367, 909-924.  
17080418 S.E.McDowell, N.Spacková, J.Sponer, and N.G.Walter (2007).
Molecular dynamics simulations of RNA: an in silico single molecule approach.
  Biopolymers, 85, 169-184.  
17507660 S.V.Steinberg, and Y.I.Boutorine (2007).
G-ribo motif favors the formation of pseudoknots in ribosomal RNA.
  RNA, 13, 1036-1042.  
17464286 T.J.Wilson, A.C.McLeod, and D.M.Lilley (2007).
A guanine nucleobase important for catalysis by the VS ribozyme.
  EMBO J, 26, 2489-2500.  
16432262 A.Nehdi, and J.P.Perreault (2006).
Unbiased in vitro selection reveals the unique character of the self-cleaving antigenomic HDV RNA sequence.
  Nucleic Acids Res, 34, 584-592.  
16345112 A.R.Feldman, E.K.Leung, A.J.Bennet, and D.Sen (2006).
The RNA-cleaving bipartite DNAzyme is a distinctive metalloenzyme.
  Chembiochem, 7, 98.  
16690998 A.T.Perrotta, T.S.Wadkins, and M.D.Been (2006).
Chemical rescue, multiple ionizable groups, and general acid-base catalysis in the HDV genomic ribozyme.
  RNA, 12, 1282-1291.  
16937241 J.E.Johnson, K.R.Julien, and C.G.Hoogstraten (2006).
Alternate-site isotopic labeling of ribonucleotides for NMR studies of ribose conformational dynamics in RNA.
  J Biomol NMR, 35, 261-274.  
16940529 J.Zhang, G.Zhang, R.Guo, B.A.Shapiro, and A.E.Simon (2006).
A pseudoknot in a preactive form of a viral RNA is part of a structural switch activating minus-strand synthesis.
  J Virol, 80, 9181-9191.  
16990549 K.Salehi-Ashtiani, A.Lupták, A.Litovchick, and J.W.Szostak (2006).
A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene.
  Science, 313, 1788-1792.  
16859740 M.Martick, and W.G.Scott (2006).
Tertiary contacts distant from the active site prime a ribozyme for catalysis.
  Cell, 126, 309-320.
PDB codes: 2goz 3zd5
16617077 M.V.Krasovska, J.Sefcikova, K.Réblová, B.Schneider, N.G.Walter, and J.Sponer (2006).
Cations and hydration in catalytic RNA: molecular dynamics of the hepatitis delta virus ribozyme.
  Biophys J, 91, 626-638.  
16513845 M.Łegiewicz, A.Wichłacz, B.Brzezicha, and J.Ciesiołka (2006).
Antigenomic delta ribozyme variants with mutations in the catalytic core obtained by the in vitro selection method.
  Nucleic Acids Res, 34, 1270-1280.  
16601203 T.J.Wilson, J.Ouellet, Z.Y.Zhao, S.Harusawa, L.Araki, T.Kurihara, and D.M.Lilley (2006).
Nucleobase catalysis in the hairpin ribozyme.
  RNA, 12, 980-987.  
16600865 W.Yang, J.Y.Lee, and M.Nowotny (2006).
Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity.
  Mol Cell, 22, 5.  
16100266 A.W.Van Wynsberghe, and Q.Cui (2005).
Comparison of mode analyses at different resolutions applied to nucleic acid systems.
  Biophys J, 89, 2939-2949.  
15919196 D.M.Lilley (2005).
Structure, folding and mechanisms of ribozymes.
  Curr Opin Struct Biol, 15, 313-323.  
15941360 D.W.Staple, and S.E.Butcher (2005).
Pseudoknots: RNA structures with diverse functions.
  PLoS Biol, 3, e213.  
16138302 H.M.Al-Hashimi (2005).
Dynamics-based amplification of RNA function and its characterization by using NMR spectroscopy.
  Chembiochem, 6, 1506-1519.  
15870731 J.A.Doudna, and J.R.Lorsch (2005).
Ribozyme catalysis: not different, just worse.
  Nat Struct Mol Biol, 12, 395-402.  
16408062 J.A.Doudna (2005).
Chemical biology at the crossroads of molecular structure and mechanism.
  Nat Chem Biol, 1, 300-303.  
15956979 M.J.Fedor, and J.R.Williamson (2005).
The catalytic diversity of RNAs.
  Nat Rev Mol Cell Biol, 6, 399-412.  
16407982 S.A.Strobel (2005).
Ribonucleic general acid.
  Nat Chem Biol, 1, 5-6.  
15811793 S.A.Woodson (2005).
Metal ions and RNA folding: a highly charged topic with a dynamic future.
  Curr Opin Chem Biol, 9, 104-109.  
16407993 S.R.Das, and J.A.Piccirilli (2005).
General acid catalysis by the hepatitis delta virus ribozyme.
  Nat Chem Biol, 1, 45-52.  
15963891 S.R.Holbrook (2005).
RNA structure: the long and the short of it.
  Curr Opin Struct Biol, 15, 302-308.  
15324800 M.Egli (2004).
"Deoxyribo nanonucleic acid"; antiparallel, parallel, and unparalleled.
  Chem Biol, 11, 1027-1029.  
15556400 M.Egli (2004).
Nucleic acid crystallography: current progress.
  Curr Opin Chem Biol, 8, 580-591.  
15574498 M.Marino (2004).
Biography of Jennifer A. Doudna.
  Proc Natl Acad Sci U S A, 101, 16987-16989.  
15625232 R.Ting, J.M.Thomas, L.Lermer, and D.M.Perrin (2004).
Substrate specificity and kinetic framework of a DNAzyme with an expanded chemical repertoire: a putative RNaseA mimic that catalyzes RNA hydrolysis independent of a divalent metal cation.
  Nucleic Acids Res, 32, 6660-6672.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.