Record Information
Version2.0
Creation Date2010-05-25 21:38:23 UTC
Update Date2014-12-24 20:26:31 UTC
Accession NumberT3D3771
Identification
Common NameRestrictocin (Aspergillus restrictus)
ClassProtein
DescriptionRestrictocin is a protein mycotoxin produced by the fungi Aspergillus giganteus and Aspergillus restrictus. It is a highly specific ribotoxin and inhibits protein synthesis by cleaving the 28S RNA of eukaryotic ribosomes. (1, 4)
Compound Type
  • Amide
  • Amine
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
  • Protein
Protein StructureT3d3771
Synonyms
Synonym
Restrictocin
Ribonuclease mitogillin
Chemical FormulaNot Available
Average Molecular Mass19595.005 g/mol
CAS Registry Number1406-72-0
SequenceNot Available
Chemical Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceClear solution.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility>10 mg/mL
LogPNot Available
Predicted PropertiesNot Available
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (5)
Mechanism of ToxicityRestrictocin is a highly specific ribotoxin that inhibits protein synthesis by cleaving a single phosphodiester bond in the sarcin/ricin loop (SRL) of the 23S−28S rRNA of eukaryotic ribosomes. The sequence around this cleavage site is a binding site for elongation factors, and is conserved in all cytoplasmic ribosomes. In order to cleave this site, restrictocin binds to the rRNA by forming an electrostatic complex using specific residues on its active site face. This cleavage prevents the binding of elongation factors to the ribosome, halts protein synthesis, and eventually leads to apoptotic cell death. (1, 2, 3)
MetabolismFree toxin may be removed by opsonization via the reticuloendothelial system (primarily the liver and kidneys) or it may be degraded through cellular internalization via the lysosomes. Lysosomes are membrane-enclosed organelles that contain an array of digestive enzymes, including several proteases.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesRestrictocin is a protein mycotoxin produced by the fungi Aspergillus giganteus and Aspergillus restrictus. (1)
Minimum Risk LevelNot Available
Health EffectsRestrictocin is a cytotoxic ribotoxin, causing cell death by inactivating eukaryotic ribosomes. (4)
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound IDNot Available
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDP67876
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB ID1AQZ
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Yang X, Moffat K: Insights into specificity of cleavage and mechanism of cell entry from the crystal structure of the highly specific Aspergillus ribotoxin, restrictocin. Structure. 1996 Jul 15;4(7):837-52. [8805570 ]
  2. Korennykh AV, Plantinga MJ, Correll CC, Piccirilli JA: Linkage between substrate recognition and catalysis during cleavage of sarcin/ricin loop RNA by restrictocin. Biochemistry. 2007 Nov 6;46(44):12744-56. Epub 2007 Oct 12. [17929942 ]
  3. Plantinga MJ, Korennykh AV, Piccirilli JA, Correll CC: Electrostatic interactions guide the active site face of a structure-specific ribonuclease to its RNA substrate. Biochemistry. 2008 Aug 26;47(34):8912-8. doi: 10.1021/bi800592g. Epub 2008 Aug 2. [18672906 ]
  4. Martinez-Ruiz A, Kao R, Davies J, Martinez del Pozo A: Ribotoxins are a more widespread group of proteins within the filamentous fungi than previously believed. Toxicon. 1999 Nov;37(11):1549-63. [10482390 ]
  5. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. RNA
References
  1. Yang X, Moffat K: Insights into specificity of cleavage and mechanism of cell entry from the crystal structure of the highly specific Aspergillus ribotoxin, restrictocin. Structure. 1996 Jul 15;4(7):837-52. [8805570 ]
  2. Korennykh AV, Plantinga MJ, Correll CC, Piccirilli JA: Linkage between substrate recognition and catalysis during cleavage of sarcin/ricin loop RNA by restrictocin. Biochemistry. 2007 Nov 6;46(44):12744-56. Epub 2007 Oct 12. [17929942 ]
  3. Plantinga MJ, Korennykh AV, Piccirilli JA, Correll CC: Electrostatic interactions guide the active site face of a structure-specific ribonuclease to its RNA substrate. Biochemistry. 2008 Aug 26;47(34):8912-8. doi: 10.1021/bi800592g. Epub 2008 Aug 2. [18672906 ]