| Autor: |
Masaru Goto, Shoko Higashi, Taro Ohba, Rena Kawata, Kazuki Nagatsu, Saori Suzuki, Eric V. Anslyn, Ryota Saito |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Biochemical and biophysical research communications. 627 |
| ISSN: |
1090-2104 |
| Popis: |
Ricin toxin A-chain (RTA), a toxic protein from Ricinus communis, inactivates ribosomes to induce toxicity. The active site of RTA consists of two binding pockets. Many studies have focused on developing RTA inhibitors that can simultaneously bind to these critical pockets; however, almost all the inhibitors developed so far interact with only one pocket. In the present study, we discovered that pterin-7-carboxamides with aromatic l-amino acid pendants interacted with the active site of the enzyme in a 2-to-1 mode, where one inhibitor molecule bound to the primary pocket and the second one entered the secondary pocket in the active site of RTA. X-ray crystallographic analysis of inhibitor/RTA complexes revealed that the conformational changes of Tyr80 and Asn122 in RTA were critical for triggering the entry of inhibitor molecules into the secondary pocket of the RTA active site. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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