4Q2V
Crystal Structure of Ricin A chain complexed with Baicalin inhibitor
Summary for 4Q2V
| Entry DOI | 10.2210/pdb4q2v/pdb |
| Descriptor | Ricin, 5,6-dihydroxy-4-oxo-2-phenyl-4H-chromen-7-yl beta-D-glucopyranosiduronic acid (3 entities in total) |
| Functional Keywords | mixed alpha/beta structure, ribosome-inactivating, baicalin complex, ribosome, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Ricinus communis (Castor bean) |
| Total number of polymer chains | 1 |
| Total formula weight | 31701.57 |
| Authors | |
| Primary citation | Dong, J.,Zhang, Y.,Chen, Y.,Niu, X.,Zhang, Y.,Li, R.,Yang, C.,Wang, Q.,Li, X.,Deng, X. Baicalin inhibits the lethality of ricin in mice by inducing protein oligomerization. J.Biol.Chem., 290:12899-12907, 2015 Cited by PubMed Abstract: Toxic ribosome-inactivating proteins abolish cell viability by inhibiting protein synthesis. Ricin, a member of these lethal proteins, is a potential bioterrorism agent. Despite the grave challenge posed by these toxins to public health, post-exposure treatment for intoxication caused by these agents currently is unavailable. In this study, we report the identification of baicalin extracted from Chinese herbal medicine as a compound capable of inhibiting the activity of ricin. More importantly, post-exposure treatment with baicalin significantly increased the survival of mice poisoned by ricin. We determined the mechanism of action of baicalin by solving the crystal structure of its complex with the A chain of ricin (RTA) at 2.2 Å resolution, which revealed that baicalin interacts with two RTA molecules at a novel binding site by hydrogen bond networks and electrostatic force interactions, suggesting its role as molecular glue of the RTA. Further biochemical and biophysical analyses validated the amino acids directly involved in binding the inhibitor, which is consistent with the hypothesis that baicalin exerts its inhibitory effects by inducing RTA to form oligomers in solution, a mechanism that is distinctly different from previously reported inhibitors. This work offers promising leads for the development of therapeutics against ricin and probably other ribosome-inactivating proteins. PubMed: 25847243DOI: 10.1074/jbc.M114.632828 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.198 Å) |
Structure validation
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