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

scholarly journals Functional divergence between the two P1–P2 stalk dimers on the ribosome in their interaction with ricin A chain

2014 ◽  
Vol 460 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Przemysław Grela ◽  
Xiao-Ping Li ◽  
Marek Tchórzewski ◽  
Nilgun E. Tumer
Keyword(s):  
Functional Divergence ◽  
Wild Type ◽  
Ricin A Chain ◽  
Yeast Ribosomes ◽  
A Chain ◽  
Wild Type Yeast ◽  
Ricin A

Wild-type yeast ribosomes and ribosomes bearing only the P1B–P2A dimer bound to the ricin A chain better and were more susceptible to depurination and toxicity than ribosomes bearing only the P1A–P2B dimer, indicating that the two stalk dimers differ in their function.

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.

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

X-ray analysis of substrate analogs in the ricin A-chain active site

1992 ◽  
Vol 227 (4) ◽  
pp. 1136-1145 ◽  
Author(s):  
Arthur F. Monzingo ◽  
Jon D. Robertus
Keyword(s):  
Active Site ◽  
Ricin A Chain ◽  
X Ray ◽  
Substrate Analogs ◽  
A Chain ◽  
Ricin A
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