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Information on EC 4.6.1.23 - ribotoxin
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4.6.1.23 ribotoxinIUBMB Comments
Ribotoxins are rRNA endonucleases that catalyse the cleavage of the phosphodiester bond between guanosine and adenosine residues at one specific position in 28S rRNA. The enzyme secreted by Aspergillus giganteus specifically cleaves rat 28S rRNA between G4325 and A4326 and displays cytotoxic activity toward animal cells. It can also act on bacterial rRNAs. The enzyme catalyses a two-stage endonucleolytic cleavage. The first reaction produces 5'-hydroxy-phosphooligonucletides and 3'-phosphooligonucleotides ending with 2',3'-cyclic phosphodiester, which are released from the enzyme. The enzyme then hydrolyses these cyclic compounds in a second reaction that takes place only when all the susceptible 3',5'-phosphodiester bonds have been cyclised. The second reaction is a reversal of the first reaction using the hydroxyl group of water instead of the 5'-hydroxyl group of ribose. The overall process is that of a phosphorus-oxygen lyase followed by hydrolysis to form the 3'-nucleotides.
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Word Map
- 4.6.1.23
- rrnas
- aspergillus
-
phosphodiester
-
ribonucleolytic
- ricin
-
cytotoxin
- fumigatus
-
ribosome-inactivating
- giganteus
- restrictus
- aspergillosis
- srl
- immunotoxins
-
depurination
- n-glycosidase
-
ribotoxic
- tetraloop
- medicine
- agrocybe
-
gaga
-
alpha-fragment
- a-chain
-
hirsutella
- aegerita
-
sarcin-ricin
- oligoribonucleotide
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
+
=
+
a 28S rRNA containing guanosine-adenosine pair
+
=
an [RNA fragment]-3'-adenosine-3'-phosphate
+
a 5'-hydroxy-guanosine-3'-[RNA fragment]
Synonyms
alpha-sarcin, restrictocin, ribotoxin, mitogillin, ageritin, ribonuclease alpha-sarcin, rrna endonuclease, alpha-sarcin-like ribotoxin restrictocin, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alpha-sarcin
EC 3.1.27.10
-
-
formerly
-
alpha-sarcin
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a 28S rRNA containing guanosine-adenosine pair + H2O = an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-hydroxy-guanosine-3'-[RNA fragment]
overall reaction
-
-
-
a 28S rRNA containing guanosine-adenosine pair = an [RNA fragment]-3'-adenosine-2',3'-cyclophosphate + a 5'-hydroxy-guanosine-3'-[RNA fragment]
(1a)
-
-
-
an [RNA fragment]-3'-adenosine-2',3'-cyclophosphate + H2O = an [RNA fragment]-3'-adenosine-3'-phosphate
(1b)
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
endoribonuclease reaction
-
-
-
-
hydrolysis
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
[28S-rRNA]-guanosine-adenosine 5'-hydroxy-guanosine-ribonucleotide-3'-[RNA fragment]-lyase (cyclicizing; [RNA fragment]-3'-adenosine-2',3'-cyclophosphate-forming and hydrolysing)
Ribotoxins are rRNA endonucleases that catalyse the cleavage of the phosphodiester bond between guanosine and adenosine residues at one specific position in 28S rRNA. The enzyme secreted by Aspergillus giganteus specifically cleaves rat 28S rRNA between G4325 and A4326 and displays cytotoxic activity toward animal cells. It can also act on bacterial rRNAs. The enzyme catalyses a two-stage endonucleolytic cleavage. The first reaction produces 5'-hydroxy-phosphooligonucletides and 3'-phosphooligonucleotides ending with 2',3'-cyclic phosphodiester, which are released from the enzyme. The enzyme then hydrolyses these cyclic compounds in a second reaction that takes place only when all the susceptible 3',5'-phosphodiester bonds have been cyclised. The second reaction is a reversal of the first reaction using the hydroxyl group of water instead of the 5'-hydroxyl group of ribose. The overall process is that of a phosphorus-oxygen lyase followed by hydrolysis to form the 3'-nucleotides.
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CAS REGISTRY NUMBER
COMMENTARY
1407-48-3
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
23S rRNA + H2O
?
-
cleavage of sarcin-ricin loop of 23S rRNA inhibits in vitro translation, slightly affects binding of elongation factor Tu ternary complex to the ribosome, inhibits elongation factor G binding, and consequently GTP hydrolysis and mRNA-tRNA translocation
-
-
?
23S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
-
-
-
?
Escherichia coli 23S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
-
-
-
-
?
Escherichia coli 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
rabbit 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
-
-
-
?
rabbit reticulocyte 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
-
-
-
?
rabbit ribosomes + H2O
?
ribosomes isolated from reticulocyte lysate
-
-
?
Rattus norvegicus 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
-
alpha-sarcin hydrolyzes a phosphodiester bond on the 3' side of a guanine residue 393 nucleotides from the 3' end. The alpha-sarcin domain is composed of a purine-rich sequence of 14 highly conserved nucleotides
-
-
?
Saccharomyces cerevisiae 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
Saccharomyces cerevisiae rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
-
-
-
?
yeast 26 S RNA + H2O
?
-
alpha-sarcin cleaves the phosphodiester bond between the guanine residue at position 3025 and the adenine residue at position 3026
-
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
-
-
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
-
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
human rhabdomyosarcoma 28S rRNA
-
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
mini-stem-loop RNA
-
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
rat liver 28S rRNA
-
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
rat liver 28S rRNA
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
rat liver 28S rRNA
-
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
-
-
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
rat liver 28S rRNA
-
?
28 S rRNA + H2O
alpha-fragment from the 3' end of 28S rRNA
-
human rhabdomyosarcoma 28S rRNA
-
-
?
ApA + H2O
3'-AMP + adenosine
-
reaction of alpha-sarcin on ApA is composed of 2 steps, transphosphorylation adenosine + 2',3'-cyclic adenosine monophosphate are the reaction products, followed by hydrolysis of the cyclic mononucleotide, producing 3'-AMP
-
-
?
Escherichia coli 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
-
-
-
-
?
Escherichia coli 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
-
-
-
?
Escherichia coli 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
Aspergillus giganteus MH18894
-
-
-
-
?
GpA + H2O
3'-GMP
-
hydrolysis of the 3'-5' phosphodiester bond of the substrate yields 2',3'-cyclic adenosine mononucleotide, this intermediate is converted into the corresponding 3'-monophosphate derivative as the final product of the reaction
-
-
?
GpA + H2O
3'-GMP
-
hydrolysis of the 3'-5' phosphodiester bond of the substrate yields 2',3'-cyclic adenosine mononucleotide, this intermediate is converted into the corresponding 3'-monophosphate derivative as the final product of the reaction
-
-
?
RNA + H2O
?
-
hydrolyzes naked RNA at purines in both single-and double-stranded regions
-
-
?
RNA + H2O
?
hydrolyzes naked RNA at purines in both single-and double-stranded regions
-
-
?
RNA + H2O
?
-
with total rRNA as substrate alpha-sarcin causes extensive progressive digestion of nucleic acids
-
-
?
rRNA + H2O
?
-
-
646298, 646299, 646300, 646301, 646302, 646303, 646304, 646305, 646306, 646307, 646308, 646309, 646310, 646311, 646312, 646314, 646315, 646316, 646318, 646319, 646320, 646321
-
-
?
rRNA + H2O
?
-
-
-
-
?
Saccharomyces cerevisiae 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
-
-
-
-
?
Saccharomyces cerevisiae 28S rRNA containing guanosine-adenosine pair + H2O
an [RNA fragment]-3'-adenosine-3'-phosphate + a 5'-a hydroxy-guanosine-3'-[RNA fragment]
Aspergillus giganteus MH18894
-
-
-
-
?
supercoiled double-stranded DNA + H2O
nicked circular conformation of DNA
-
-
-
-
?
supercoiled double-stranded DNA + H2O
nicked circular conformation of DNA
-
no effect on linear DNA
at low concentrations, further into a linear form at high concentrations
?
additional information
?
-
-
alpha-sarcin cleavage site lies between a guanosine and adenosine residue in the sequence AGUACGAG AGGAAG
-
-
?
additional information
?
-
-
specific ribonuclease activity against ribosomal RNA causes ribosome disruption and subsequent protein biosynthesis inhibition
-
-
?
additional information
?
-
-
mechanism of action is hydrolysis of a phosphodiester bond between G-4325 and A-4326 of rat 28S ribosomal RNA producing an alpha-fragment from the 3' end of 28S rRNA
-
-
?
additional information
?
-
-
alpha-sarcin modifies neighbouring sites in the sarcin/ricin loop of 28S rRNA, destroying the necessary dynamic flexibility of the ribosome, inhibiting the elongation factor assisted steps of the elongation cycle
-
-
?
additional information
?
-
-
induction of cell death via apoptosis
-
-
?
additional information
?
-
deletion mutant delta(7-22) exhibits activity against naked rRNA and synthetic substrates but lacks the specific ability of the wild-type protein to degrade rRNA in intact ribosomes
-
-
?
additional information
?
-
-
arginine 121 is a crucial residue for the specific cytotoxic activity of alpha-sarcin
-
-
?
additional information
?
-
-
alpha-sarcin site nucleotide sequence is identical in the large rRNAs of cytoplasmic ribosomes from a range of evolutionary diverse organisms, evolutionarily conserved in all eukaryotes and prokaryotes so far tested
-
-
?
additional information
?
-
-
alpha-sarcin site nucleotide sequence is identical in the large rRNAs of cytoplasmic ribosomes from a range of evolutionary diverse organisms, evolutionarily conserved in all eukaryotes and prokaryotes so far tested
-
-
?
additional information
?
-
-
alpha-sarcin site nucleotide sequence is identical in the large rRNAs of cytoplasmic ribosomes from a range of evolutionary diverse organisms, evolutionarily conserved in all eukaryotes and prokaryotes so far tested
-
-
?
additional information
?
-
alpha-sarcin site nucleotide sequence is identical in the large rRNAs of cytoplasmic ribosomes from a range of evolutionary diverse organisms, evolutionarily conserved in all eukaryotes and prokaryotes so far tested
-
-
?
additional information
?
-
-
with rat liver ribosomes or 60S ribosomal subunits as substrates alpha-sarcin cleaves a single oligonucleotide of about 488 residues, the alpha-fragment from the 3' end of 28 S rRNA, 40 S ribosomal subunits are not affected by the enzyme, hydrolysis of DNA requires large amounts of the toxin
-
-
?
additional information
?
-
-
cytotoxic protein that inhibits eukaryotic elongation factor 1 catalyzed binding of aminoacyl-tRNA to ribosomes as a result of cleaving a fragment from the large RNA in the 60 S ribosomal subunit
-
-
?
additional information
?
-
-
cytotoxic protein that inhibits eukaryotic elongation factor 1 catalyzed binding of aminoacyl-tRNA to ribosomes as a result of cleaving a fragment from the large RNA in the 60 S ribosomal subunit
-
-
?
additional information
?
-
-
leucine 145 plays a key role for determining the specificity of the ribosome-inactivating activity of the protein
-
-
?
additional information
?
-
-
the ribosome-inactivating proteins alpha-sarcin targets the ribosomal sarcin/ricin loop, specific recognition and cleavage. The eukaryotic ribosomal stalk directly interacts with several members of the N-glycosidase family, favoring their disruption of the sarcin/ricin loop, overview. alpha-Sarcin does not interact with the P1/P2 C-terminal peptide SDDDMGFGLFD
-
-
?
additional information
?
-
-
the rate of cleavage is comparable both in presence and in absence of ribosomal proteins. More complete cleavage is observed in the absence of ribosomal proteins
-
-
?
additional information
?
-
-
specific ribonuclease activity against ribosomal RNA causes ribosome disruption and subsequent protein biosynthesis inhibition
-
-
?
additional information
?
-
-
alpha-sarcin site nucleotide sequence is identical in the large rRNAs of cytoplasmic ribosomes from a range of evolutionary diverse organisms, evolutionarily conserved in all eukaryotes and prokaryotes so far tested
-
-
?
additional information
?
-
-
mechanism of action is hydrolysis of a phosphodiester bond between G-4325 and A-4326 of rat 28S ribosomal RNA producing an alpha-fragment from the 3' end of 28S rRNA
-
-
?
additional information
?
-
-
acts as a cyclizing ribonuclease
-
-
?
additional information
?
-
-
acts as a cyclizing ribonuclease
-
-
?
additional information
?
-
-
induction of cell death via apoptosis
-
-
?
additional information
?
-
Aspergillus giganteus MH18894
-
the rate of cleavage is comparable both in presence and in absence of ribosomal proteins. More complete cleavage is observed in the absence of ribosomal proteins
-
-
?
additional information
?
-
ageritin shows specific ribonucleolytic activity against the ribosomal sarcin-ricin loop in a rabbit reticulocytes assay
-
-
?
additional information
?
-
-
hybridization, pH 7.55, 350 mM of monovalent cations, 10 mM MgCl2, 37°C
-
-
?
additional information
?
-
-
cleaving a specific adenine from the highly conserved alpha-sarcin loop of the host 28S ribosomal RNA
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
the ribosome-inactivating proteins alpha-sarcin targets the ribosomal sarcin/ricin loop, specific recognition and cleavage. The eukaryotic ribosomal stalk directly interacts with several members of the N-glycosidase family, favoring their disruption of the sarcin/ricin loop, overview. alpha-Sarcin does not interact with the P1/P2 C-terminal peptide SDDDMGFGLFD
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
KCl
Mg2+
additional information
KCl
-
at low salt concentrations less than 5 mM maximum of cleavage rate
KCl
-
at low salt concentrations of less than 5 mM the enzyme has its maximum cleavage rate
Mg2+
ageritin strongly binds magnesium ions with low micromolar affinity, KD value 308 nM
additional information
activity is strongly metal-dependent and completely suppressed in the presence of EDTA
additional information
ageritin's ribonucleolytic activity requires the presence of divalent cations, with a maximum activation in the presence of zinc ions
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
elongation factor G
the transitory binding of elongation factor G and GDP to the ribosome inhibits the rate of alpha-sarcin cleavage. The stabilization of this binding with fusidic acid completely prevents alpha-sarcin cleavage
-
GDP
the transitory binding of elongation factor G and GDP to the ribosome inhibits the rate of alpha-sarcin cleavage. The stabilization of this binding with fusidic acid completely prevents alpha-sarcin cleavage
Sodium dodecyl sulfate
-
reversible inhibition of ribonuclease activity, irreversible inhibition of deoxyribonuclease activity
Thiostrepton
irreversible binding of the antibiotic thiostrepton to the Escherichia coll ribosome decreases the rate of cleavage by alpha-sarcin approximately 2fold
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ribosomal stalk
-
the eukaryotic ribosomal stalk directly interacts with several members of the N-glycosidase family, favoring their disruption of the SRL
-
additional information
-
P1 protein isozymes P1alphaP2beta and P1betaP2alpha are acidic proteins that are extremely dynamic, including their exchange with the cytoplasmic pool, their C-terminal regions being responsible for the interaction, recruitment, and regulation of supernatant translation factors and ribosome-inactivating proteins like ricin and trichosanthin, but alpha-sarcin does not interact with the P1/P2 C-terminal peptide SDDDMGFGLFD
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Ultrastructural changes induced by alpha-sarcin in a human pulmonary tumor grown in naked mice.
Aspergillosis
Analysis of the major proteins secreted by the human opportunistic pathogen Aspergillus fumigatus under in vitro conditions.
Aspergillosis
Secretion of a potential virulence factor, a fungal ribonucleotoxin, during human aspergillosis infections.
Aspergillosis
Use of recombinant mitogillin for improved serodiagnosis of Aspergillus fumigatus-associated diseases.
Aspergillosis, Allergic Bronchopulmonary
Immunodominant peptide epitopes of allergen, Asp f 1 from the fungus Aspergillus fumigatus.
Brain Neoplasms
Purification, characterization and cytotoxicity assessment of Ageritin: The first ribotoxin from the basidiomycete mushroom Agrocybe aegerita.
Breast Neoplasms
Immunoconjugate generation between the ribosome inactivating protein restrictocin and an anti-human breast carcinoma MAB.
Carcinoma
Biochemical, cytotoxic and pharmacokinetic properties of an immunotoxin composed of a mouse monoclonal antibody Fib75 and the ribosome-inactivating protein alpha-sarcin from Aspergillus giganteus.
Carcinoma
Preparation of an engineered safer immunotoxin against colon carcinoma based on the ribotoxin hirsutellin A.
Colorectal Neoplasms
Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin ?-sarcin in nude mice bearing human colorectal cancer xenografts.
Colorectal Neoplasms
Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin ?-Sarcin- or RNase T1-Based Immunotoxins.
Infections
Analysis of the major proteins secreted by the human opportunistic pathogen Aspergillus fumigatus under in vitro conditions.
Infections
Beauveria bassiana ribotoxin inhibits insect immunity responses to facilitate infection via host translational blockage.
Infections
Entry of feline calicivirus is dependent on clathrin-mediated endocytosis and acidification in endosomes.
Infections
Virulence of Aspergillus fumigatus double mutants lacking restriction and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis.
Influenza in Birds
Effects of edeine, hygromycin B and alpha-Sarcin on influenza virus reproduction.
Influenza, Human
Effects of edeine, hygromycin B and alpha-Sarcin on influenza virus reproduction.
Invasive Pulmonary Aspergillosis
Aspergillus fumigatus and Its Allergenic Ribotoxin Asp f I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology.
Invasive Pulmonary Aspergillosis
Construction and pathogenicity of Aspergillus fumigatus mutants that do not produce the ribotoxin restrictocin.
Invasive Pulmonary Aspergillosis
Effects of alkaline protease or restrictocin deficient mutants of Aspergillus fumigatus on human polymorphonuclear leukocytes.
Invasive Pulmonary Aspergillosis
Use of recombinant mitogillin for improved serodiagnosis of Aspergillus fumigatus-associated diseases.
Mycoses
Characterization of the Aspergillus fumigatus chitosanase CsnB and evaluation of its potential use in serological diagnostics.
Neoplasms
Deletion of the NH2-terminal beta-hairpin of the ribotoxin alpha-sarcin produces a nontoxic but active ribonuclease.
Neoplasms
Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin ?-sarcin in nude mice bearing human colorectal cancer xenografts.
Neoplasms
Evaluation of mitogillin (NSC-69529) in the treatment of naturally occurring canine neoplasms.
Neoplasms
Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin ?-Sarcin- or RNase T1-Based Immunotoxins.
Neoplasms
Kinetic study of the cytotoxic effect of alpha-sarcin, a ribosome inactivating protein from Aspergillus giganteus, on tumour cell lines: protein biosynthesis inhibition and cell binding.
Neoplasms
Noncytotoxic ribonuclease, RNase T1, induces tumor cell death via hemagglutinating virus of Japan envelope vector.
Neoplasms
Purification, characterization and cytotoxicity assessment of Ageritin: The first ribotoxin from the basidiomycete mushroom Agrocybe aegerita.
Neoplasms
Study of the interaction between the antitumour protein alpha-sarcin and phospholipid vesicles.
Neoplasms
Toxicity and membrane perturbation properties of the ribotoxin-like protein Ageritin.
Neoplasms
Ultrastructural changes induced by alpha-sarcin in a human pulmonary tumor grown in naked mice.
Neuroblastoma
Ageritin from poplar mushrooms: scale-up purification and cytotoxicity towards undifferentiated and differentiated SH-SY5Y cells.
Rhabdomyosarcoma
Cytotoxic mechanism of the ribotoxin alpha-sarcin. Induction of cell death via apoptosis.
Rotavirus Infections
Rotaviruses induce an early membrane permeabilization of MA104 cells and do not require a low intracellular Ca2+ concentration to initiate their replication cycle.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.076
SRL
-
sarcin/ricin loop in ribosomal RNA, 10 mM Tris-HCl, 0-5 mM KCl, pH 7-7.4, 37°C
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
specific activity 18200 units/mg, 1 unit is the amount of protein causing 50% inhibition of protein synthesis in 0.001 ml of rabbit-reticulocyte lysate system
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5
-
optimum for ApA degradation , secondary activity maximum at neutral pH 7.0, about 30% of the maximum value
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
MDH 18894
-
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
both mutant and wild-type variants of alpha-sarcin localize to the nucleus and cytoplasm, where they colocalize with ribosomal marker RPS6
brenda
alpha-sarcin proteins are exclusively localized in large and small vacuoles
brenda
-
both mutant and wild-type variants of alpha-sarcin localize to the nucleus and cytoplasm, where they colocalize with ribosomal marker RPS6
brenda
sequence lacks a signal peptide for classical secretion
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
mutations in alpha-sarcin, which impair alpha-sarcin's ability to inhibit protein synthesis, do not affect its cytotoxicity. The mutants are unable to activate Jun N-terminal kinase, thus the sarcin-ricin loop remains intact indicating that the alpha-sarcin mutants are catalytically inactive
physiological function
additional information
physiological function
-
alpha-sarcin cleaves the large 23S rRNA at the universally conserved sarcin-ricin loop leading to complete inactivation of the ribosome and cellular death. alpha-Sarcin-treated ribosomes show no defects in mRNA and tRNA binding, peptide-bond formation and sparsomycin-dependent translocation, whereas activity of elongation factor G is strongly impaired
physiological function
-
both alpha-sarcin and ricin transfected cells demonstrate a dose-dependent decrease in viability at 48 hours, whereby ricin is more effective at low doses (50 ng) than alpha-sarcin. At concentrations greater than 250 ng, no further reduction in viability and approximately 20% of the cells remain viable. Direct cytoplasmic expression of alpha-sarcin and ricin in mammalian cells is cytotoxic: exogenous expression of both alpha-sarcin and ricin in HeLa cells results in decreased viability within 48 hours. Both alpha-sarcin and ricin induce cell death at similar rates, with ricin exhibiting slightly enhanced cytotoxicity. Direct expression of alpha-sarcin in Cos-7 cells also results in cytotoxicity. Although protein synthesis inhibition likely contributes to cell death, it is not required. alpha-Sarcin can promote cell death through a mechanism that is independent of rRNA cleavage and Jun N-terminal kinase activation
physiological function
-
alpha-sarcin is cytotoxic to many tumor cell lines as well as dividing and non-dividing cells, the cytotoxicity of the protein toxin is regulated by protein splicin. alpha-Sarcin splicing is dependent on rapamycin, is inducible with rapid kinetics, and triggers apoptosis in HeLa cells. Spliced alpha-sarcin inhibits protein synthesis
physiological function
-
the fungal ribotoxin alpha-sarcin is one of the most potent and specific toxins known. It is small, protease-resistant, thermostable and highly efficient towards the inactivation of ribosomes
physiological function
-
the inactivation exerted by alpha-sarcin is independent of the composition of the ribosomal stalk
physiological function
ageritin displayed antibacterial activity against Micrococcus lysodeikticus, activity against the tobacco mosaic virus RNA, endonuclease activity against a supercoiled plasmid, nuclease activity against genomic DNA, cytotoxicity to COLO 320, HeLa, and Raji cells by promoting apoptosis, and antifungal activity against the green mold Penicillium digitatum
physiological function
ageritin heterologously expressed in Escherichia coli shows a strong toxicity against Aedes aegypti larvae yet not against nematodes. Entomotoxicity of ageritin is mediated by ribonucleolytic cleavage
physiological function
purified ageritin is able to inhibit protein synthesis in a rabbit reticulocyte lysate, with an IC50 value of 133 pM
physiological function
-
the fungal ribotoxin alpha-sarcin is one of the most potent and specific toxins known. It is small, protease-resistant, thermostable and highly efficient towards the inactivation of ribosomes
-
additional information
-
the P1/P2 C-terminal peptide SDDDMGFGLFD does not interact with alpha-sarcin
additional information
-
the recombinant fusion enzyme scFvA33alphasarcin shows high specific toxicity against GPA33-positive tumoral colon carcinoma cell lines, cellular binding and internalization of recombinant enzyme fusion construct scFvA33alphasarcin, overview
additional information
-
the recombinant fusion enzyme scFvA33alphasarcin shows high specific toxicity against GPA33-positive tumoral colon carcinoma cell lines, cellular binding and internalization of recombinant enzyme fusion construct scFvA33alphasarcin, overview
-
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). RNAS_ASPGI
177
0
19724
Swiss-Prot
Secretory Pathway (Reliability: 1)
RNAG_AGRAE
156
0
16910
Swiss-Prot
other Location (Reliability: 2)
RNAS_ASPGI
177
0
19724
Swiss-Prot
Secretory Pathway (Reliability: 1)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
17000
45000
-
x * 45000, recombinant His-tagged enzyme fusion construct scFvA33alphasarcin, SDS-PAGE
additional information
-
15N-1H residual dipolar coupling NMR, alkyl poly(ethylene glycol)/alcohol mixture, 1 mM, pH 6.0, 25°C
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
dimeric form fails to inactivate ribosomes as well as to hydrolyze mini-stem-loop RNA, but is an effective ribonuclease in situ
monomer
?
-
x * 45000, recombinant His-tagged enzyme fusion construct scFvA33alphasarcin, SDS-PAGE
?
-
x * 45000, recombinant His-tagged enzyme fusion construct scFvA33alphasarcin, SDS-PAGE
-
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
alpha-sarcin is synthesized in an inactive precursor form and segregated and matured in the membrane compartment
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
15N-1H residual dipolar coupling NMR, alkyl poly(ethylene glycol)/alcohol mixture, 1 mM, pH 6.0, 25°C, 24 Hz
-
alpha-sarcin three-dimensional structure determined by X-ray diffraction of single crystals of the toxin
-
circular dichroism studies. The protein contains about 40% of periodic structures, mainly located at both extremes of the polypeptide chain. beta-Turns and aperiodic conformation appear at the central part of the molecule
-
to 2.1 A resolution. The tertiary structure of the substrate RNA is important in protein-RNA recognition, fitting closely into the concavity of the presumed binding site
homology modeling of structure. Ageritin has a structural core consisting of an antiparallel beta-sheet and an adjacent long alpha-helix, typical of ribotoxins and RNase T1 family
modeling of the catalytic metal binding site of ageritin, made of the putative triad Asp68, Asp70 and His77. Ageritin has the structure and function of an RNase but a Mg2+/Zn2+-dependent mechanism of action
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E96A
-
mutagenised using the T7-GEN TM in vitro mutagenesis kit, 80% less cytotoxity to HeLa cells
H137Q
L145F
-
oligonucleotide-site directed mutagenesis, retains cytotoxic activity
N54A
mutation in a conserved residue located in loop 2 of the protein, decrease in melting temperature. About 65% of wild-type activity with ribosomes and ribosomal loop RNA
N54D
mutation in a conserved residue located in loop 2 of the protein, decrease in melting temperature. About 60% of wild-type activity with ribosomes and ribosomal loop RNA
N54Q
mutation in a conserved residue located in loop 2 of the protein, decrease in melting temperature. About 24% and 68% of wild-type activity with ribosomes and ribosomal loop RNA, respectively
N54S
mutation in a conserved residue located in loop 2 of the protein, decrease in melting temperature. About 28 and 49% of wild-type activity with ribosomes and ribosomal loop RNA, respectively
N54Y
mutation in a conserved residue located in loop 2 of the protein, decrease in melting temperature. Loss of activity
R121Q
Y48F
mutant is produced in Escherichia coli and purified to homogeneity (ca. 3 mg/l of original bacterial culture)
E96A
-
mutagenised using the T7-GEN TM in vitro mutagenesis kit, 80% less cytotoxity to HeLa cells
-
H137Q
K63D
-
mutant with decreased activity for sarcin/ricin loop-cleavage of ribosomes
R21D/K28D
-
mutant with decreased activity for sarcin/ricin loop-cleavage of ribosomes
R21D/K28D/K63D
-
mutant with decreased activity for sarcin/ricin loop-cleavage of ribosomes
K11E
-
slightly lower specific ribonucleolytic activity than wild type (assayed against intact ribosomes)
K17E
-
slightly lower specific ribonucleolytic activity than wild type (assayed against intact ribosomes)
K21E
-
slightly lower specific ribonucleolytic activity than wild type (assayed against intact ribosomes)
R22E
-
slightly lower specific ribonucleolytic activity than wild type (assayed against intact ribosomes)
H137Q
additional information
H137Q
-
similar to the wild-type and mutant R121Q, this mutant is cytotoxic in HeLa cells or Cos-7 cells in a dose-dependent manner. Both GFP and luciferase expression are not inhibited
R121Q
-
despite its reduced catalytic ability in vitro, the mutant is cytotoxic in HeLa cells or Cos-7 cells in a dose-dependent manner, that is only slightly reduced from that observed for wild-type. Both GFP and luciferase expression are not inhibited
H137Q
-
a variant which is completely devoid of cytotoxicity and ribonucleolytic activity, retains the wildtype native conformation
H137Q
-
a variant which is completely devoid of cytotoxicity and ribonucleolytic activity, retains the wildtype native conformation
-
additional information
-
method development for engineering of alpha-sarcin splicing, overview. The splicing constructs, NSar-VMAN-FKBP and FRB-VMAC-CSar splice poorly, and the intein-alpha-sarcin splice junctions interfere with splicing
additional information
-
pentadecanucleotide ONS5 binds to target sequence ECAS171 with high affinity to form heteroduplex to occur via strand displacement pathway
additional information
-
pentadecanucleotide ONS5 bounds to target sequence ECAS171 with high affinity to form heteroduplex to occur via strand displacement pathway
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3 - 8.5
additional information
-
five different pH-induced conformational transitions are detected. Two of them, at pH 2.5 and 10.2, are denaturing transitions
752836
3 - 8.5
-
out of this pH range denaturation occurs, about half maximal activity at pH 3.8 and pH 6.5
646310
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
52.6
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
in guanidinium hydrochloride, half-completion of denaturing transition occurs at 5.1 M
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
alpha-sarcin cDNA cloned by consecutive annealing of overlapping primers followed by ligation into XhoI- and HindIII-sites in pcDNA3.1 or pcDNA3-mychis vector (C-terminal MycHis tag). alpha-Sarcin cDNA cloned into 3 × FLAG pMSCV to obtain a N-terminal 3 × Flag tagged version of alpha-sarcin. Expression of wild-type and mutant constructs in HeLa or Cos-7 cells
-
cloning of the genomic alpha-sarcin gene pGEM-T/FL-alpha plasmid, construction of the alpha-sarcin gene and its mutants by PCR, using genomic DNA as template
-
doxycycline-inducible intracellular expression of wild-type alpha-sarcin in Saccharomyces cerevisiae strain W303 and in strains deficient for P1 or P2 protein, wild-type alpha-sarcin is lethal in all wild-type yeast clones, while 30% and 80% of resistant clones are obtained for the DELTAP1alphaP2beta and DELTAP2 strains, respectively
-
expression in Escherichia coli
recombinant expression of FLAG3-tagged alpha-sarcin in HeLa cells, alpha-sarcin splicing is incduced by and dependent on rapamycin, is inducible with rapid kinetics, and triggers apoptosis in the cytoplasm of HeLa cells
-
recombinant extracellular His-tagged enzyme fusion construct scFvA33alphasarcin from expression in Pichia pastoris strain KM71 by nickel affinity chromatgraphy
-
the His-tagged enzyme is fused to the single-chain variable fragment (scFv) of the monoclonal antibody that targets GPA33, the construct scFvA33alphasarcin is expressed in Pichia pastoris strain KM71 using the AOX1 promoter, subcloning in Escherichia coli DH5aF cells, and secretion to the medium
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
alpha-sarcin inhibits growth of tumors by inhibition of protein synthesis, protein induces apoptosis in tumor cells after internalization via endocytosis, alpha-sarcin is cytotoxic for normal human cells and for many tumor cell lines, particulary sarcoma and carcinoma, it shows a selective, high level of toxicity against cells with altered or damaged cell membranes, it is a promising candidate for the treatment of cancer and viral infections such as AIDS
medicine
alpha-sarcin inhibits growth of tumors by inhibition of protein synthesis, protein induces apoptosis in tumor cells after internalization via endocytosis, alpha-sarcin is cytotoxic for normal human cells and for many tumor cell lines, particulary sarcoma and carcinoma, it shows a selective, high level of toxicity against cells with altered or damaged cell membranes, it is a promising candidate for the treatment of cancer and viral infections such as AIDS
medicine
-
the recombinant fusion enzyme scFvA33alphasarcin shows high specific toxicity against GPA33-positive tumoral cell lines providing scientific evidence to sustain that scFvA33alphasarcin is a good immunotherapeutic candidate against GPA33-positive colon carcinomas
medicine
attachment of alpha-sarcin to a monoclonal mouse IgG2 antibody Fib75 to synthesize an immunotoxin. The alpha-sarcin immunotoxin exerts toxic effects in tissue culture against the EJ human bladder carcinoma cell line, expressing the antigen recognised by the Fib75 antibody, inhibiting the incorporation of [3H]leucine by 50% at a concentration of 0.46 nM. The cytotoxic effects of the alpha-sarcin immunotoxin are indistinguishable from those of a Fib75 immunotoxin made with ricin A chain. Fib75-alpha-sarcin is cleared from the circulation of the rat with biphasic kinetics following intravenous administration. The alpha- and beta-phase half-lives are 0.8 h and 6 h, respectively, similar to the serum half-lives of analogous Fib75 immunotoxins made with ribosome-inactivating proteins derived from plants
medicine
enzyme displays cytotoxity against tumour cells. The ribotoxin dose, able to inhibit by 50% the mitochondrial redox activity of C6 glial cells, is equal to 4.58 microg/ml (0.316 microM). A ribotoxin dose of 8.41 microg/ml inhibits by 50% human SK-N-BE(2)-C neuroblastoma cells and of 9.46 microg/ml U-251 glioma cells
medicine
-
the recombinant fusion enzyme scFvA33alphasarcin shows high specific toxicity against GPA33-positive tumoral cell lines providing scientific evidence to sustain that scFvA33alphasarcin is a good immunotherapeutic candidate against GPA33-positive colon carcinomas
-
medicine
-
alpha-sarcin inhibits growth of tumors by inhibition of protein synthesis, protein induces apoptosis in tumor cells after internalization via endocytosis, alpha-sarcin is cytotoxic for normal human cells and for many tumor cell lines, particulary sarcoma and carcinoma, it shows a selective, high level of toxicity against cells with altered or damaged cell membranes, it is a promising candidate for the treatment of cancer and viral infections such as AIDS
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Endo, Y.; Wool, I.G.
The site of action of alpha-sarcin on eukaryotic ribosomes. The sequence at the alpha-sarcin cleavage site in 28 S ribosomal ribonucleic acid
J. Biol. Chem.
257
9054-9060
1982
Aspergillus giganteus
brenda
Endo, Y.; Huber, P.W.; Wool, I.G.
The ribonuclease activity of the cytotoxin alpha-sarcin. The characteristics of the enzymatic activity of alpha-sarcin with ribosomes and ribonucleic acids as substrates
J. Biol. Chem.
258
2662-2667
1983
Aspergillus giganteus
brenda
Wool, I.G.
The mechanism of the action of the cytotoxic nuclease alpha-sarcin and its use to analyze ribosome structure
Trends Biochem. Sci.
9
14-17
1984
Aspergillus giganteus
-
brenda
Stirpe, F.; Bailey, S.; Miller, S.P.; Bodley, J.W.
Modification of ribosomal RNA by ribosome-inactivating proteins from plants
Nucleic Acids Res.
16
1349-1357
1988
Aspergillus giganteus
brenda
Ling, J.; Liu, W.; Wang, T.P.
Cleavage of supercoiled double-stranded DNA by several ribosome-inactivating proteins in vitro
FEBS Lett.
345
143-146
1994
Aspergillus giganteus
brenda
Gasset, M.; Mancheno, J.M.; Laynez, J.; Lacadena, J.; Fernandez-Ballester, G.; Martinez del Pozo, A.; Onaderra, M.; Gavilanes, J.G.
Thermal unfolding of the cytotoxin alpha-sarcin: phospholipid binding induces destabilization of the protein structure
Biochim. Biophys. Acta
1252
126-134
1995
Aspergillus giganteus, Aspergillus giganteus MDH 18894
brenda
Lacadena, J.; Mancheno, J.M.; Martinez-Ruiz, A.; Martinez del Pozo, A.; Gasset, M.; Onaderra, M.; Gavilanes, J.G.
Substitution of histidine-137 by glutamine abolishes the catalytic activity of the ribosome-inactivating protein alpha-sarcin
Biochem. J.
309
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1995
Aspergillus giganteus, Aspergillus giganteus MDH 18894
brenda
Campos-Olivas, R.; Bruix, M.; Santoro, J.; Martinez del Pozo, A.; Lacadena, J.; Gavilanes, J.G.; Rico, M.
Structural basis for the catalytic mechanism and substrate specificity of the ribonuclease alpha-sarcin
FEBS Lett.
399
163-165
1996
Aspergillus giganteus
brenda
Cheung, J.I.; Wang, Y.R.; Lin, A.
Substrate specificity of monomeric and dimeric alpha-sarcin
FEBS Lett.
386
60-64
1996
Aspergillus giganteus
brenda
Sylvester, I.D.; Roberts, L.M.; Lord, J.M.
Characterization of prokaryotic recombinant Aspergillus ribotoxin alpha-sarcin
Biochim. Biophys. Acta
1358
53-60
1997
Aspergillus giganteus
brenda
Hao, J.J.; Xu, Y-z.; Geng, C.d.; Liu, W.Y.; Wang, E.d; Gong, Z.z.; Ulbrich, N.
Purification of alpha-sarcin and an antifungal protein from Aspergillus giganteus by blue sepharose CL-6B affinity chromatography
Protein Expr. Purif.
14
295-301
1998
Aspergillus giganteus, Aspergillus giganteus MDH 18894
brenda
Lacadena, J.; Martinez del Pozo, A.; Lacadena, V.; Martinez-Ruiz, A.; Mancheno, J.M.; Onaderra, M.; Gavilanes, J.G.
The cytotoxin alpha-sarcin behaves as a cyclizing ribonuclease
FEBS Lett.
424
46-48
1998
Aspergillus giganteus, Aspergillus giganteus MDH 18894
brenda
Perez-Canadillas, J.M.; Campos-Olivas, R.; Lacadena, J.; Martinez del Pozo, A.; Gavilanes, J.G.; Santoro, J.; Rico, M.; Bruix, M.
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
1998
Aspergillus giganteus
brenda
Lacadena, J.; Martinez del Pozo, A.; Martinez-Ruiz, A.; Perez-Canadillas, J.M.; Bruix, M.; Mancheno, J.M.; Onaderra, M.; Gavilanes, J.G.
Role of histidine-50, glutamic acid-96, and histidine-137 in the ribonucleolytic mechanism of the ribotoxin alpha-sarcin
Proteins
37
474-484
1999
Aspergillus giganteus, Aspergillus giganteus MDH 18894
brenda
Hwu, L.; Huang, K.; Chen, D.; Lin, A.
The action mode of the ribosome-inactivating protein alpha-sarcin
J. Biomed. Sci.
7
420-428
2000
Aspergillus giganteus
brenda
Perez-Canadillas, J.M.; Santoro, J.; Campos-Olivas, R.; Lacadena, J.; Martinez del Pozo, A.; Gavilanes, J.G.; Rico, M.; Bruix, M.
The highly refined solution structure of the cytotoxic ribonuclease alpha-sarcin reveals the structural requirements for substrate recognition and ribonucleolytic activity
J. Mol. Biol.
299
1061-1073
2000
Aspergillus giganteus (P00655)
brenda
Xu, Y.Z.; Liu, W.Y.
Effects of the active aldehyde group generated by RNA N-glycosidase in the sarcin/ricin domain of rat 28S ribosomal RNA on peptide elongation
Biol. Chem.
381
113-119
2000
Aspergillus giganteus
brenda
Masip, M.; Lacadena, J.; Mancheno, J.M.; Onaderra, M.; Martinez-Ruiz, A.; Martinez del Pozo, A.; Gavilanes, J.G.
Arginine 121 is a crucial residue for the specific cytotoxic activity of the ribotoxin alpha-sarcin
Eur. J. Biochem.
268
6190-6196
2001
Aspergillus giganteus
brenda
Olmo, N.; Turnay, J.; Gonzalez de Buitrago, G.; Lopez de Silanes, I.; Gavilanes, J.G.; Lizarbe, M.A.
Cytotoxic mechanism of the ribotoxin alpha-sarcin. Induction of cell death via apoptosis
Eur. J. Biochem.
268
2113-2123
2001
Aspergillus giganteus, Aspergillus giganteus MDH 18894
brenda
Garcia-Ortega, L.; Masip, M.; Mancheno, J.M.; Onaderra, M.; Lizarbe, M.A.; Garcia-Mayoral, M.F.; Bruix, M.; Martinez del Pozo, A.; Gavilanes, J.G.
Deletion of the NH2-terminal beta-hairpin of the ribotoxin alpha-sarcin produces a nontoxic but active ribonuclease
J. Biol. Chem.
277
18632-18639
2002
Aspergillus giganteus (P00655)
brenda
Larsson, S.L.; Sloma, M.S.; Nygard, O.
Conformational changes in the structure of domains II and V of 28S rRNA in ribosomes treated with the translational inhibitors ricin or alpha-sarcin
Biochim. Biophys. Acta
1577
53-62
2002
Aspergillus giganteus
brenda
Liu, R.s.; Huang, H.; Yang, Q.; Liu, W.Y.
Purification of alpha-sarcin and an antifungal protein from mold (Aspergillus giganteus) by chitin affinity chromatography
Protein Expr. Purif.
25
50-58
2002
Aspergillus giganteus, Aspergillus giganteus MDH 18894
brenda
Masip, M.; Garcia-Ortega, L.; Olmo, N.; Garcia-Mayoral, M.F.; Perez-Canadillas, J.M.; Bruix, M.; Onaderra, M.; Martinez del Pozo, A.; Gavilanes, J.G.
Leucine 145 of the ribotoxin alpha-sarcin plays a key role for determining the specificity of the ribosome-inactivating activity of the protein
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12
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2003
Aspergillus giganteus
brenda
Perez-Canadilllas, J.M.; Garcia-Mayoral, M.F.; Laurents, D.V.; Martinez del Pozo, A.; Gavilanes, J.G.; Rico, M.; Bruix, M.
Tautomeric state of alpha-sarcin histidines. Ndelta tautomers are a common feature in the active site of extracellular microbial ribonucleases
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534
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2003
Aspergillus giganteus
brenda
Garcia-Mayoral, M.F.; Pantoja-Uceda, D.; Santoro, J.; Martinez del Pozo, A.; Gavilanes, J.G.; Rico, M.; Bruix, M.
Refined NMR structure of alpha-sarcin by 15N-1H residual dipolar couplings
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34
1057-1065
2005
Aspergillus giganteus
brenda
Korennykh, A.V.; Piccirilli, J.A.; Correll, C.C.
The electrostatic character of the ribosomal surface enables extraordinarily rapid target location by ribotoxins
Nat. Struct. Mol. Biol.
13
436-443
2006
Aspergillus restrictus
brenda
Petyuk, V.A.; Serikov, R.N.; Vlassov, V.V.; Zenkova, M.A.
Hybridization of antisense oligonucleotides with alpha-sarcin loop region of Escherichia coli 23S rRNA
Nucleosides Nucleotides Nucleic Acids
23
895-906
2004
Escherichia coli
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Jandhyala, D.M.; Ahluwalia, A.; Obrig, T.; Thorpe, C.M.
ZAK: a MAP3Kinase that transduces Shiga toxin and ricin induced proinflammatory cytokine expression
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10
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Escherichia coli
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Alvarez-Garcia, E.; Martinez-del-Pozo, A.; Gavilanes, J.G.
Role of the basic character of alpha-sarcins NH2-terminal beta-hairpin in ribosome recognition and phospholipid interaction
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481
37-44
2009
Fungi
brenda
Alvarez-Garcia, E.; Garcia-Ortega, L.; Verdun, Y.; Bruix, M.; Martinez del Pozo, A.; Gavilanes, J.G.
Tyr-48, a conserved residue in ribotoxins, is involved in the RNA-degrading activity of alpha-sarcin
Biol. Chem.
387
535-541
2006
Aspergillus giganteus (P00655)
brenda
Alvarez-Garcia, E.; Alegre-Cebollada, J.; Batanero, E.; Monedero, V.; Perez-Martinez, G.; Garcia-Fernandez, R.; Gavilanes, J.G.; Martinez Del Pozo, A.
Lactococcus lactis as a vehicle for the heterologous expression of fungal ribotoxin variants with reduced IgE-binding affinity
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134
1-8
2008
Lactococcus lactis, Lactococcus lactis MG1363
brenda
Herrero-Galan, E.; Lacadena, J.; Martinez Del Pozo, A.; Boucias, D.G.; Olmo, N.; Onaderra, M.; Gavilanes, J.G.
The insecticidal protein hirsutellin A from the mite fungal pathogen Hirsutella thompsonii is a ribotoxin
Proteins
72
217 - 228
2008
Aspergillus giganteus (P00655)
brenda
Alford, S.; Pearson, J.; Carette, A.; Ingham, R.; Howard, P.
alpha-Sarcin catalytic activity is not required for cytotoxicity
BMC Biochem.
10
9-9
2009
Aspergillus giganteus
brenda
Garcia-Ortega, L.; Alvarez-Garcia, E.; Gavilanes, J.G.; Martinez-Del-Pozo, A.; Joseph, S.
Cleavage of the sarcin-ricin loop of 23S rRNA differentially affects EF-G and EF-Tu binding
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38
4108-4119
2010
Aspergillus giganteus
brenda
Alford, S.C.; OSullivan, C.; Obst, J.; Christie, J.; Howard, P.L.
Conditional protein splicing of alpha-sarcin in live cells
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10
831-837
2014
Aspergillus giganteus
brenda
Carreras-Sangra, N.; Tome-Amat, J.; Garcia-Ortega, L.; Batt, C.A.; Onaderra, M.; Martinez-del-Pozo, A.; Gavilanes, J.G.; Lacadena, J.
Production and characterization of a colon cancer-specific immunotoxin based on the fungal ribotoxin alpha-sarcin
Protein Eng. Des. Sel.
25
425-435
2012
Aspergillus giganteus, Aspergillus giganteus MDH18894
brenda
He, K.; Zhou, H.R.; Pestka, J.J.
Mechanisms for ribotoxin-induced ribosomal RNA cleavage
Toxicol. Appl. Pharmacol.
265
10-18
2012
Aspergillus giganteus
brenda
Citores, L.; Ragucci, S.; Ferreras, J.M.; Di Maro, A.; Iglesias, R.
Ageritin, a ribotoxin from poplar mushroom (Agrocybe aegerita) with defensive and antiproliferative activities
ACS Chem. Biol.
14
1319-1327
2019
Cyclocybe aegerita (C0HLG3)
brenda
Tayyrov, A.; Azevedo, S.; Herzog, R.; Vogt, E.; Arzt, S.; Luethy, P.; Mueller, P.; Ruehl, M.; Hennicke, F.; Kuenzler, M.
Heterologous production and functional characterization of ageritin, a novel type of ribotoxin highly expressed during fruiting of the edible mushroom Agrocybe aegerita
Appl. Environ. Microbiol.
85
e01549
2019
Cyclocybe aegerita (C0HLG3)
brenda
Miller, S.P.; Bodley, J.W.
Alpha-sarcin cleaves ribosomal RNA at the alpha-sarcin site in the absence of ribosomal proteins
Biochem. Biophys. Res. Commun.
154
404-410
1988
Aspergillus giganteus, Aspergillus giganteus MH18894
brenda
Landi, N.; Pacifico, S.; Ragucci, S.; Iglesias, R.; Piccolella, S.; Amici, A.; Di Giuseppe, A.M.A.; Di Maro, A.
Purification, characterization and cytotoxicity assessment of ageritin The first ribotoxin from the basidiomycete mushroom Agrocybe aegerita
Biochim. Biophys. Acta
1861
1113-1121
2017
Cyclocybe aegerita (C0HLG3)
brenda
Ruggiero, A.; Garcia-Ortega, L.; Ragucci, S.; Russo, R.; Landi, N.; Berisio, R.; Di Maro, A.
Structural and enzymatic properties of Ageritin, a novel metal-dependent ribotoxin-like protein with antitumor activity
Biochim. Biophys. Acta
1862
2888-2894
2018
Cyclocybe aegerita (C0HLG3)
brenda
Martinez del Pozo, A.; Gasset, M.; Onaderra, M.; Gavilanes, J.G.
Conformational study of the antitumor protein alpha-sarcin
Biochim. Biophys. Acta
953
280-288
1988
Aspergillus giganteus
brenda
Siemer, A.; Masip, M.; Carreras, N.; Garcia-Ortega, L.; Onaderra, M.; Bruix, M.; Del Pozo, A.M.; Gavilanes, J.G.
Conserved asparagine residue 54 of alpha-sarcin plays a role in protein stability and enzyme activity
Biol. Chem.
385
1165-1170
2004
Aspergillus giganteus (P00655)
brenda
Wawrzynczak, E.J.; Henry, R.V.; Cumber, A.J.; Parnell, G.D.; Derbyshire, E.J.; Ulbrich, N.
Biochemical, cytotoxic and pharmacokinetic properties of an immunotoxin composed of a mouse monoclonal antibody Fib75 and the ribosome-inactivating protein alpha-sarcin from Aspergillus giganteus
Eur. J. Biochem.
196
203-209
1991
Aspergillus giganteus (P00655), Aspergillus giganteus
brenda
Marchant, A.; Hartley, M.R.
Mutational studies on the alpha-sarcin loop of Escherichia coli 23S ribosomal RNA
Eur. J. Biochem.
226
141-147
1994
Aspergillus giganteus
brenda
Ruggiero, A.; Garcia-Ortega, L.; Moreira, M.; Ragucci, S.; Landi, N.; Di Maro, A.; Berisio, R.
Binding and enzymatic properties of ageritin, a fungal ribotoxin with novel zinc-dependent function
Int. J. Biol. Macromol.
136
625-631
2019
Cyclocybe aegerita (C0HLG3)
brenda
Landi, N.; Ragucci, S.; Russo, R.; Pedone, P.V.; Chambery, A.; Di Maro, A.
Structural insights into nucleotide and protein sequence of Ageritin a novel prototype of fungal ribotoxin
J. Biochem.
165
415-422
2019
Cyclocybe aegerita (C0HLG3)
brenda
Chan, Y.L.; Endo, Y.; Wool, I.G.
The sequence of the nucleotides at the alpha-sarcin cleavage site in rat 28 S ribosomal ribonucleic acid
J. Biol. Chem.
258
12768-12770
1983
Aspergillus giganteus
brenda
Miller, S.P.; Bodley, J.W.
Alpha-sarcin cleavage of ribosomal RNA is inhibited by the binding of elongation factor G or thiostrepton to the ribosome
Nucleic Acids Res.
19
1657-1660
1991
Aspergillus giganteus (P00655)
brenda
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
4
837-852
1996
Aspergillus restrictus (P67876), Aspergillus restrictus
brenda
Endo, Y.; Oka, T.; Tsurugi, K.; Natori, Y.
The biosynthesis of a cytotoxic protein, alpha-sarcin, in a mold Aspergillus giganteus. I. Synthesis of prepro- and pro-alpha-sarcin in vitro
Tokushima J. Exp. Med.
40
1-6
1993
Aspergillus giganteus (P00655), Aspergillus giganteus
brenda
Endo, Y.; Oka, T.; Yokota, S.; Tsurugi, K.; Natori, Y.
The biosynthesis of a cytotoxic protein, alpha-sarcin, in a mold of Aspergillus giganteus. II. Maturation of precursor form of alpha-sarcin in vivo
Tokushima J. Exp. Med.
40
7-12
1993
Aspergillus giganteus (P00655), Aspergillus giganteus
brenda
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