Effects of Chemical Modification of Arginine Residues Outside the Active Site Cleft of Ricin A-Chain on Its RNAN-Glycosidase Activity for Ribosomes

1994 ◽  
Vol 58 (4) ◽  
pp. 716-721 ◽  
Author(s):  
Keiichi Watanabe ◽  
Hiromichi Dansako ◽  
Noriaki Asada ◽  
Masahiko Sakai ◽  
Gunki Funatsu
Keyword(s):  
Chemical Modification ◽  
Active Site ◽  
Ricin A Chain ◽  
Glycosidase Activity ◽  
Active Site Cleft ◽  
Arginine Residues ◽  
A Chain ◽  
Ricin A

scholarly journals Arginine Residues on the Opposite Side of the Active Site Stimulate the Catalysis of Ribosome Depurination by Ricin A Chain by Interacting with the P-protein Stalk

2013 ◽  
Vol 288 (42) ◽  
pp. 30270-30284 ◽  
Author(s):  
Xiao-Ping Li ◽  
Peter C. Kahn ◽  
Jennifer Nielsen Kahn ◽  
Przemysław Grela ◽  
Nilgun E. Tumer
Keyword(s):  
Active Site ◽  
Ricin A Chain ◽  
P Protein ◽  
Arginine Residues ◽  
A Chain ◽  
Ricin A

Alteration of an amino acid residue outside the active site of the ricin A chain reduces its toxicity towards yeast ribosomes

1991 ◽  
Vol 230 (1-2) ◽  
pp. 81-90 ◽  
Author(s):  
Jane H. Gould ◽  
Martin R. Hartley ◽  
Philip C. Welsh ◽  
Deborah K. Hoshizaki ◽  
Arthur Frankel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Residue ◽  
Active Site ◽  
Ricin A Chain ◽  
Yeast Ribosomes ◽  
A Chain ◽  
Ricin A

A BRIEF COMMUNICATION

2009 ◽  
Vol 234 (8) ◽  
pp. 961-966 ◽  
Author(s):  
Alexander Weng ◽  
Cornelia Görick ◽  
Matthias F. Melzig
Keyword(s):  
Diphtheria Toxin ◽  
Culture Conditions ◽  
Ricin A Chain ◽  
Enhancing Effect ◽  
Glycosidase Activity ◽  
Mechanism Of Toxicity ◽  
A Chain ◽  
Cell Culture Conditions ◽  
Ricin A ◽  
Dependent Mechanism

Saponins are amphiphilic substances consisting of a hydrophobic backbone with one or two hydrophilic sugar units. Recently it was shown that saponinum album (SA) from Gypsophila paniculata L. enhanced cytotoxicity of a saporin-based chimeric toxin (up to 385,000-fold) as well as the toxicity of saporin (up to 100,000-fold) with N-glycosidase activity. Previously we have shown that toxicity of other N-glycosidases such as ricin A-chain, nigrin b, and toxins such as diphtheria toxin or microcystin-LR was not enhanced by SA. This points to a specific SA-dependent mechanism of toxicity enhancement on saporin and saporin-based toxins. Although the cytotoxicity enhancing effect was observed in up to 10 different cell lines, nothing is known about the kinetic of SA under cell culture conditions. Therefore SA was titrated, and the uptake respective liberation profile of SA was investigated in ECV-304 cells. Treatment of cells with [3H]-SA leads to an immediate uptake of saponin molecules. After cells were saturated with [3H]-SA, a first equilibrium (first eq.) was reached. The first eq. was disturbed by washing until a second equilibrium was reached between the activity observed within cells and that seen in the supernatant. After a further extensive washing, a small portion of saponin molecules remained durable associated with the cell. This portion was sufficient to induce a drastic toxicity enhancement on saporin indicating a long-lasting sensitization of cells against the toxin.

Structure and Activity of an Active Site Substitution of Ricin A Chain†,‡

Biochemistry ◽  
1996 ◽  
Vol 35 (34) ◽  
pp. 11098-11103 ◽  
Author(s):  
Philip J. Day ◽  
Stephen R. Ernst ◽  
Arthur E. Frankel ◽  
Arthur F. Monzingo ◽  
John M. Pascal ◽  
...  
Keyword(s):  
Active Site ◽  
Ricin A Chain ◽  
A Chain ◽  
Structure And Activity ◽  
Ricin A

The effect of mutations surrounding and within the active site on the catalytic activity of ricin A chain

2003 ◽  
Vol 271 (1) ◽  
pp. 153-162 ◽  
Author(s):  
Catherine J. Marsden ◽  
Vilmos Fülöp ◽  
Philip J. Day ◽  
J. Michael Lord
Keyword(s):  
Catalytic Activity ◽  
Active Site ◽  
Ricin A Chain ◽  
A Chain ◽  
Ricin A

scholarly journals Peptide Mimics of the Ribosomal P Stalk Inhibit the Activity of Ricin A Chain by Preventing Ribosome Binding

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 371 ◽  
Author(s):  
Xiao-Ping Li ◽  
Jennifer Kahn ◽  
Nilgun Tumer
Keyword(s):  
Amino Acids ◽  
Binding Site ◽  
Active Site ◽  
Ribosome Binding Site ◽  
Ricin A Chain ◽  
Ribosome Binding ◽  
P Proteins ◽  
A Chain ◽  
Ribosomal P ◽  
Ricin A

Ricin A chain (RTA) depurinates the sarcin/ricin loop (SRL) by interacting with the C-termini of the ribosomal P stalk. The ribosome interaction site and the active site are located on opposite faces of RTA. The interaction with P proteins allows RTA to depurinate the SRL on the ribosome at physiological pH with an extremely high activity by orienting the active site towards the SRL. Therefore, if an inhibitor disrupts RTA–ribosome interaction by binding to the ribosome binding site of RTA, it should inhibit the depurination activity. To test this model, we synthesized peptides mimicking the last 3 to 11 amino acids of P proteins and examined their interaction with wild-type RTA and ribosome binding mutants by Biacore. We measured the inhibitory activity of these peptides on RTA-mediated depurination of yeast and rat liver ribosomes. We found that the peptides interacted with the ribosome binding site of RTA and inhibited depurination activity by disrupting RTA–ribosome interactions. The shortest peptide that could interact with RTA and inhibit its activity was four amino acids in length. RTA activity was inhibited by disrupting its interaction with the P stalk without targeting the active site, establishing the ribosome binding site as a new target for inhibitor discovery.

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