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PDBsum entry 1aqz
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protein ligands Protein-protein interface(s) links
Ribotoxin PDB id
1aqz

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
142 a.a. *
Ligands
PO4 ×3
Waters ×202
* Residue conservation analysis
PDB id:
1aqz
Name: Ribotoxin
Title: Crystal structure of a highly specific aspergillus ribotoxin, restrictocin
Structure: Restrictocin. Chain: a, b. Other_details: inorganic phosphate group at the active site
Source: Aspergillus restrictus. Organism_taxid: 5064
Resolution:
1.70Å     R-factor:   0.237     R-free:   0.177
Authors: X.Yang,K.Moffat
Key ref:
X.Yang and K.Moffat (1996). Insights into specificity of cleavage and mechanism of cell entry from the crystal structure of the highly specific Aspergillus ribotoxin, restrictocin. Structure, 4, 837-852. PubMed id: 8805570
Date:
04-Aug-97     Release date:   12-Nov-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
P67876  (RNMG_ASPRE) -  Ribonuclease mitogillin from Aspergillus restrictus
Seq:
Struc: 		176 a.a.
142 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.1.27.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
Structure 4:837-852 (1996)
PubMed id: 8805570  
 
 
Insights into specificity of cleavage and mechanism of cell entry from the crystal structure of the highly specific Aspergillus ribotoxin, restrictocin.
X.Yang, K.Moffat.
 
  ABSTRACT  
 
BACKGROUND: Restriction, a highly specific ribotoxin made by the fungus Aspergillus restrictus, cleaves a single phosphodiester bond in the 28S RNA of eukaryotic ribosomes, inhibiting protein synthesis. The sequence around this cleavage site is a binding site for elongation factors, and is conserved in all cytoplasmic ribosomes. The catalytic mechanism of restrictocin and the reasons for its high substrate specificity are unknown. No structure has been determined for any other member of the Aspergillus ribotoxin family. RESULTS: The crystal structure of restrictocin was determined at 2.1 A resolution by single isomorphous replacement and anomalous scattering techniques, and refined to 1.7 A resolution using synchrotron Laue data. The structural core of the protein, in which a three-turn alpha helix is packed against a five-stranded antiparallel beta sheet, can be well aligned with that of ribonuclease T1. Large positively charged peripheral loops near the active site construct a platform with a concave surface for RNA binding. CONCLUSIONS: Restriction appears to combine the catalytic components of T1 ribonucleases with the base recognition components of Sa ribonucleases. Modeling studies using an NMR structure of an RNA substrate analog suggest that the tertiary structure of the substrate RNA is important in protein-RNA recognition, fitting closely into the concavity of the presumed binding site. We speculate that the large 39-residue loop L3, which has similarities to loops found in lectin sugar-binding domains, may be responsible for restrictocin's ability to cross cell membranes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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.  
18621419 N.Oezguen, B.Zhou, S.S.Negi, O.Ivanciuc, C.H.Schein, G.Labesse, and W.Braun (2008).
Comprehensive 3D-modeling of allergenic proteins and amino acid composition of potential conformational IgE epitopes.
  Mol Immunol, 45, 3740-3747.  
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.  
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.  
15885102 L.Garciá-Ortega, J.Lacadena, M.Villalba, R.Rodríguez, J.F.Crespo, J.Rodríguez, C.Pascual, N.Olmo, M.Oñaderra, A.M.del Pozo, and J.G.Gavilanes (2005).
Production and characterization of a noncytotoxic deletion variant of the Aspergillus fumigatus allergen Aspf1 displaying reduced IgE binding.
  FEBS J, 272, 2536-2544.  
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.  
15653429 A.Siemer, M.Masip, N.Carreras, L.García-Ortega, M.Oñaderra, M.Bruix, A.M.Del Pozo, and J.G.Gavilanes (2004).
Conserved asparagine residue 54 of alpha-sarcin plays a role in protein stability and enzyme activity.
  Biol Chem, 385, 1165-1170.  
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.  
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
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.  
12560495 O.Schrader, T.Baumstark, and D.Riesner (2003).
A mini-RNA containing the tetraloop, wobble-pair and loop E motifs of the central conserved region of potato spindle tuber viroid is processed into a minicircle.
  Nucleic Acids Res, 31, 988-998.  
11673454 J.P.Langedijk (2002).
Translocation activity of C-terminal domain of pestivirus Erns and ribotoxin L3 loop.
  J Biol Chem, 277, 5308-5314.  
12239315 J.P.Langedijk, P.A.van Veelen, W.M.Schaaper, A.H.de Ru, R.H.Meloen, and M.M.Hulst (2002).
A structural model of pestivirus E(rns) based on disulfide bond connectivity and homology modeling reveals an extremely rare vicinal disulfide.
  J Virol, 76, 10383-10392.  
12228255 J.Sevcik, L.Urbanikova, P.A.Leland, and R.T.Raines (2002).
X-ray structure of two crystalline forms of a streptomycete ribonuclease with cytotoxic activity.
  J Biol Chem, 277, 47325-47330.
PDB codes: 1mgr 1mgw
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.  
11468362 L.García-Ortega, J.Lacadena, J.M.Mancheño, M.Oñaderra, R.Kao, J.Davies, N.Olmo, Pozo AM, and J.G.Gavilanes (2001).
Involvement of the amino-terminal beta-hairpin of the Aspergillus ribotoxins on the interaction with membranes and nonspecific ribonuclease activity.
  Protein Sci, 10, 1658-1668.  
11733014 M.Masip, J.Lacadena, J.M.Mancheño, M.Oñaderra, A.Martínez-Ruiz, A.Martínez del Pozo, and J.G.Gavilanes (2001).
Arginine 121 is a crucial residue for the specific cytotoxic activity of the ribotoxin alpha-sarcin.
  Eur J Biochem, 268, 6190-6196.  
11685244 X.Yang, T.Gérczei, L.T.Glover, and C.C.Correll (2001).
Crystal structures of restrictocin-inhibitor complexes with implications for RNA recognition and base flipping.
  Nat Struct Biol, 8, 968-973.
PDB codes: 1jbr 1jbs 1jbt
11025546 C.de Antonio, A.Martínez del Pozo, J.M.Mancheño, M.Oñaderra, J.Lacadena, A.Martínez-Ruiz, J.M.Pérez-Cañadillas, M.Bruix, and J.G.Gavilanes (2000).
Assignment of the contribution of the tryptophan residues to the spectroscopic and functional properties of the ribotoxin alpha-sarcin.
  Proteins, 41, 350-361.  
10971140 L.Hwu, K.Huang, D.Chen, and A.Lin (2000).
The action mode of the ribosome-inactivating protein alpha-sarcin.
  J Biomed Sci, 7, 420-428.  
10712610 S.K.Nayak, Shveta, and J.K.Batra (2000).
Localization of the catalytic activity in restrictocin molecule by deletion mutagenesis.
  Eur J Biochem, 267, 1777-1783.  
10591106 J.Lacadena, A.Martínez del Pozo, A.Martínez-Ruiz, J.M.Pérez-Cañadillas, M.Bruix, J.M.Mancheño, M.Oñaderra, and J.G.Gavilanes (1999).
Role of histidine-50, glutamic acid-96, and histidine-137 in the ribonucleolytic mechanism of the ribotoxin alpha-sarcin.
  Proteins, 37, 474-484.  
  10194462 J.P.Latgé (1999).
Aspergillus fumigatus and aspergillosis.
  Clin Microbiol Rev, 12, 310-350.  
10212236 R.Kao, and J.Davies (1999).
Molecular dissection of mitogillin reveals that the fungal ribotoxins are a family of natural genetically engineered ribonucleases.
  J Biol Chem, 274, 12576-12582.  
9811818 C.C.Correll, A.Munishkin, Y.L.Chan, Z.Ren, I.G.Wool, and T.A.Steitz (1998).
Crystal structure of the ribosomal RNA domain essential for binding elongation factors.
  Proc Natl Acad Sci U S A, 95, 13436-13441.
PDB code: 430d
9843392 J.M.Pérez-Cañadillas, R.Campos-Olivas, J.Lacadena, A.Martínez del Pozo, J.G.Gavilanes, J.Santoro, M.Rico, and M.Bruix (1998).
Characterization of pKa values and titration shifts in the cytotoxic ribonuclease alpha-sarcin by NMR. Relationship between electrostatic interactions, structure, and catalytic function.
  Biochemistry, 37, 15865-15876.  
9767570 R.Kao, J.E.Shea, J.Davies, and D.W.Holden (1998).
Probing the active site of mitogillin, a fungal ribotoxin.
  Mol Microbiol, 29, 1019-1027.  
9761904 X.Yang, Z.Ren, and K.Moffat (1998).
Structure refinement against synchrotron Laue data: strategies for data collection and reduction.
  Acta Crystallogr D Biol Crystallogr, 54, 367-377.  
9354640 S.K.Nayak, and J.K.Batra (1997).
A single amino acid substitution in ribonucleolytic toxin restrictocin abolishes its specific substrate recognition activity.
  Biochemistry, 36, 13693-13699.  
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 code is shown on the right.

 

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