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PDBsum entry 1jbs

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protein dna_rna metals links
Hydrolase/RNA PDB id
1jbs
Jmol
Contents
Protein chains
149 a.a. *
DNA/RNA
Metals
__K ×6
Waters ×341
* Residue conservation analysis
PDB id:
1jbs
Name: Hydrolase/RNA
Title: Crystal structure of ribotoxin restrictocin and a 29-mer srd analog
Structure: 29-mer sarcin/ricin domain RNA analog. Chain: c, d. Engineered: yes. Restrictocin. Chain: a, b. Synonym: ribonuclease mitogillin. Ec: 3.1.27.-
Source: Synthetic: yes. Other_details: the sequence contains 14 highly conserved nu among all living species.. Aspergillus restrictus. Organism_taxid: 5064
Biol. unit: Tetramer (from PQS)
Resolution:
1.97Å     R-factor:   0.213     R-free:   0.257
Authors: X.Yang,T.Gerczei,L.Glover,C.C.Correll
Key ref:
X.Yang et al. (2001). Crystal structures of restrictocin-inhibitor complexes with implications for RNA recognition and base flipping. Nat Struct Biol, 8, 968-973. PubMed id: 11685244 DOI: 10.1038/nsb1101-968
Date:
06-Jun-01     Release date:   26-Oct-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P67876  (RNMG_ASPRE) -  Ribonuclease mitogillin
Seq:
Struc:
176 a.a.
149 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     metabolic process   5 terms 
  Biochemical function     hydrolase activity     5 terms  

 

 
DOI no: 10.1038/nsb1101-968 Nat Struct Biol 8:968-973 (2001)
PubMed id: 11685244  
 
 
Crystal structures of restrictocin-inhibitor complexes with implications for RNA recognition and base flipping.
X.Yang, T.Gérczei, L.T.Glover, C.C.Correll.
 
  ABSTRACT  
 
The cytotoxin sarcin disrupts elongation factor binding and protein synthesis by specifically cleaving one phosphodiester bond in ribosomes. To elucidate the molecular basis of toxin action, we determined three cocrystal structures of the sarcin homolog restrictocin bound to different analogs that mimic the target sarcin/ricin loop (SRL) structure of the rat 28S rRNA. In these structures, restrictocin contacts the bulged-G motif and an unfolded form of the tetraloop of the SRL RNA. In one structure, toxin loops guide selection of the target site by contacting the base critical for recognition (G4319) and the surrounding S-shaped backbone. In another structure, base flipping of the tetraloop enables cleavage by placing the target nucleotide in the active site with the nucleophile nearly inline for attack on the scissile bond. These structures provide the first views of how a site-specific protein endonuclease recognizes and cleaves a folded RNA substrate.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structural overview. a, Schematic of the RNA sequence showing the conserved nucleotides (boxed), tetraloop (green) and bulged-G motif (yellow). The sites of 2' modification of the stem (asterisks) and of 4325 and 4326 (plus signs) are shown. The terminal nucleotides are designed to pair and create a blunt end (red); the remainder corresponds to rat 28S nucleotides 4315 -4333 (hereafter, Escherichia coli 23S numbering is in parentheses). The two 29-mer variants (nU4325dA^4326 and mG4325dA^4326) are missing the first and the last nucleotide. When enzyme concentrations exceed that of substrates other than ribosomes, cleavage by the toxin is primarily on the 3' side of purines3. b, A ribbon drawing of the restrictocin -mG4325 (misdocked) complex showing the tetraloop (green) and bulged-G motif (yellow) of the substrate, as well as the bound potassium ions (pink).
Figure 4.
Figure 4. Implications for cleavage and recognition. a, Superposition of the structure of the scissile phosphate groups of the target nucleotide from the uncomplexed substrate SRL RNA^11 (red), the 3' splice site of a splicing endonuclease^19 (yellow) and the ground state forms of the lead-dependent22 (navy) and the hammerhead^20 (blue) ribozymes. b, Superposition of the structures of the two types of S-turn: one in the bound complex (blue) and another in the L11 -RNA complex38 (yellow).
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 968-973) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20854710 W.Yang (2011).
Nucleases: diversity of structure, function and mechanism.
  Q Rev Biophys, 44, 1.  
20852642 C.L.Ng, K.Lang, N.A.Meenan, A.Sharma, A.C.Kelley, C.Kleanthous, and V.Ramakrishnan (2010).
Structural basis for 16S ribosomal RNA cleavage by the cytotoxic domain of colicin E3.
  Nat Struct Mol Biol, 17, 1241-1246.
PDB codes: 2xfz 2xg0 2xg1 2xg2
20512980 E.Pichinuk, and D.H.Wreschner (2010).
Similarities between Argonautes and the alpha-sarcin-like ribotoxins: Implications for microRNA action.
  Protein Sci, 19, 1272-1278.  
20215430 L.García-Ortega, E.Alvarez-García, J.G.Gavilanes, A.Martínez-del-Pozo, and S.Joseph (2010).
Cleavage of the sarcin-ricin loop of 23S rRNA differentially affects EF-G and EF-Tu binding.
  Nucleic Acids Res, 38, 4108-4119.  
20223772 X.J.Lu, W.K.Olson, and H.J.Bussemaker (2010).
The RNA backbone plays a crucial role in mediating the intrinsic stability of the GpU dinucleotide platform and the GpUpA/GpA miniduplex.
  Nucleic Acids Res, 38, 4868-4876.  
19348010 A.Viegas, E.Herrero-Galán, M.Oñaderra, A.L.Macedo, and M.Bruix (2009).
Solution structure of hirsutellin A--new insights into the active site and interacting interfaces of ribotoxins.
  FEBS J, 276, 2381-2390.
PDB code: 2kaa
19920175 M.C.Ho, M.B.Sturm, S.C.Almo, and V.L.Schramm (2009).
Transition state analogues in structures of ricin and saporin ribosome-inactivating proteins.
  Proc Natl Acad Sci U S A, 106, 20276-20281.
PDB codes: 3hio 3hiq 3his 3hit 3hiv 3hiw
19346475 S.Qin, and H.X.Zhou (2009).
Dissection of the high rate constant for the binding of a ribotoxin to the ribosome.
  Proc Natl Acad Sci U S A, 106, 6974-6979.  
18214983 E.Herrero-Galán, J.Lacadena, A.Martínez del Pozo, D.G.Boucias, N.Olmo, M.Oñaderra, and J.G.Gavilanes (2008).
The insecticidal protein hirsutellin A from the mite fungal pathogen Hirsutella thompsonii is a ribotoxin.
  Proteins, 72, 217-228.  
17910059 J.J.Ellis, and S.Jones (2008).
Evaluating conformational changes in protein structures binding RNA.
  Proteins, 70, 1518-1526.  
18672906 M.J.Plantinga, A.V.Korennykh, J.A.Piccirilli, and C.C.Correll (2008).
Electrostatic interactions guide the active site face of a structure-specific ribonuclease to its RNA substrate.
  Biochemistry, 47, 8912-8918.  
18716674 S.Shazman, and Y.Mandel-Gutfreund (2008).
Classifying RNA-binding proteins based on electrostatic properties.
  PLoS Comput Biol, 4, e1000146.  
18356035 S.Yamasaki, and P.Anderson (2008).
Reprogramming mRNA translation during stress.
  Curr Opin Cell Biol, 20, 222-226.  
18824128 T.Xia (2008).
Taking femtosecond snapshots of RNA conformational dynamics and complexity.
  Curr Opin Chem Biol, 12, 604-611.  
17553832 D.Min, S.Xue, H.Li, and W.Yang (2007).
'In-line attack' conformational effect plays a modest role in an enzyme-catalyzed RNA cleavage: a free energy simulation study.
  Nucleic Acids Res, 35, 4001-4006.  
17253975 J.Lacadena, E.Alvarez-García, N.Carreras-Sangrà, E.Herrero-Galán, J.Alegre-Cebollada, L.García-Ortega, M.Oñaderra, J.G.Gavilanes, and A.Martínez del Pozo (2007).
Fungal ribotoxins: molecular dissection of a family of natural killers.
  FEMS Microbiol Rev, 31, 212-237.  
17707400 L.M.Wadley, K.S.Keating, C.M.Duarte, and A.M.Pyle (2007).
Evaluating and learning from RNA pseudotorsional space: quantitative validation of a reduced representation for RNA structure.
  J Mol Biol, 372, 942-957.  
17477546 S.Roday, S.Saen-oon, and V.L.Schramm (2007).
Vinyldeoxyadenosine in a sarcin-ricin RNA loop and its binding to ricin toxin a-chain.
  Biochemistry, 46, 6169-6182.  
16604082 A.V.Korennykh, J.A.Piccirilli, and C.C.Correll (2006).
The electrostatic character of the ribosomal surface enables extraordinarily rapid target location by ribotoxins.
  Nat Struct Mol Biol, 13, 436-443.  
16740124 E.Alvarez-García, L.García-Ortega, Y.Verdún, M.Bruix, A.Martínez del Pozo, and J.G.Gavilanes (2006).
Tyr-48, a conserved residue in ribotoxins, is involved in the RNA-degrading activity of alpha-sarcin.
  Biol Chem, 387, 535-541.  
16456030 N.Spacková, and J.Sponer (2006).
Molecular dynamics simulations of sarcin-ricin rRNA motif.
  Nucleic Acids Res, 34, 697-708.  
15812638 M.F.García-Mayoral, D.Pantoja-Uceda, J.Santoro, A.Martínez del Pozo, J.G.Gavilanes, M.Rico, and M.Bruix (2005).
Refined NMR structure of alpha-sarcin by 15N-1H residual dipolar couplings.
  Eur Biophys J, 34, 1057-1065.  
15333634 A.Martins, and S.Shuman (2004).
An RNA ligase from Deinococcus radiodurans.
  J Biol Chem, 279, 50654-50661.  
15211513 L.L.Videau, W.B.Arendall, and J.S.Richardson (2004).
The cis-Pro touch-turn: a rare motif preferred at functional sites.
  Proteins, 56, 298-309.  
15608296 L.M.Wadley, and A.M.Pyle (2004).
The identification of novel RNA structural motifs using COMPADRES: an automated approach to structural discovery.
  Nucleic Acids Res, 32, 6650-6659.  
15044731 M.F.García-Mayoral, L.García-Ortega, M.P.Lillo, J.Santoro, A.Martínez del Pozo, J.G.Gavilanes, M.Rico, and M.Bruix (2004).
NMR structure of the noncytotoxic alpha-sarcin mutant Delta(7-22): the importance of the native conformation of peripheral loops for activity.
  Protein Sci, 13, 1000-1011.
PDB code: 1r4y
14627814 C.C.Correll, J.Beneken, M.J.Plantinga, M.Lubbers, and Y.L.Chan (2003).
The common and the distinctive features of the bulged-G motif based on a 1.04 A resolution RNA structure.
  Nucleic Acids Res, 31, 6806-6818.
PDB codes: 1q93 1q96 1q9a
12592009 C.C.Correll, and K.Swinger (2003).
Common and distinctive features of GNRA tetraloops based on a GUAA tetraloop structure at 1.4 A resolution.
  RNA, 9, 355-363.
PDB code: 1msy
12824344 H.Yang, F.Jossinet, N.Leontis, L.Chen, J.Westbrook, H.Berman, and E.Westhof (2003).
Tools for the automatic identification and classification of RNA base pairs.
  Nucleic Acids Res, 31, 3450-3460.  
12493839 M.Masip, L.García-Ortega, N.Olmo, M.F.García-Mayoral, J.M.Pérez-Cañadillas, M.Bruix, M.Oñaderra, A.Martínez del Pozo, and J.G.Gavilanes (2003).
Leucine 145 of the ribotoxin alpha-sarcin plays a key role for determining the specificity of the ribosome-inactivating activity of the protein.
  Protein Sci, 12, 161-169.  
12717724 S.B.Howerton, A.Nagpal, and L.D.Williams (2003).
Surprising roles of electrostatic interactions in DNA-ligand complexes.
  Biopolymers, 69, 87-99.
PDB code: 1p20
11897788 L.Garcia-Ortega, M.Masip, J.M.Mancheño, M.Oñaderra, M.A.Lizarbe, M.F.García-Mayoral, M.Bruix, A.Martínez del Pozo, and J.G.Gavilanes (2002).
Deletion of the NH2-terminal beta-hairpin of the ribotoxin alpha-sarcin produces a nontoxic but active ribonuclease.
  J Biol Chem, 277, 18632-18639.  
11839295 X.Cheng, and R.M.Blumenthal (2002).
Cytosines do it, thymines do it, even pseudouridines do it--base flipping by an enzyme that acts on RNA.
  Structure, 10, 127-129.  
11779468 C.Hoang, and A.R.Ferré-D'Amaré (2001).
Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme.
  Cell, 107, 929-939.
PDB code: 1k8w
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.