7XZS

Crystal structure of Ricin A chain bound with (2-amino-4-oxo-3,4-dihydropteridine-7-carbonyl)-L-tyrosine

Summary for 7XZS

• Entry DOI: 10.2210/pdb7xzs/pdb
• Descriptor: Ricin A chain, (2S)-2-[(2-azanyl-4-oxidanylidene-3H-pteridin-7-yl)carbonylamino]-3-(4-hydroxyphenyl)propanoic acid, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase inhibitor, hydrolase
• Biological source: Ricinus communis (castor bean)
• Total number of polymer chains: 1
• Total formula weight: 31829.58

Authors

Goto, M.,Higashi, S.,Ohba, T.,Kawata, R.,Nagatsu, K.,Suzuki, S.,Saito, R. (deposition date: 2022-06-03, release date: 2022-12-21, Last modification date: 2023-11-29)

Primary citation

Goto, M.,Higashi, S.,Ohba, T.,Kawata, R.,Nagatsu, K.,Suzuki, S.,Anslyn, E.V.,Saito, R.
Conformational change in ricin toxin A-Chain: A critical factor for inhibitor binding to the secondary pocket.
Biochem.Biophys.Res.Commun., 627:1-4, 2022

PubMed Abstract: 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.

PubMed: 35998389
DOI: 10.1016/j.bbrc.2022.08.008

Experimental method

X-RAY DIFFRACTION (1.5 Å)