3NY6

Catalytic fragment of cholix toxin from vibrio cholerae in complex with inhibitor V30

Summary for 3NY6

• Entry DOI: 10.2210/pdb3ny6/pdb
• Related: 2Q6M 3ESS 3KI0 3KI1 3KI2 3KI3 3KI4 3KI5 3KI6 3KI7
• Descriptor: Cholix toxin, GLYCEROL, 2-[(5,6-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)sulfanyl]-N-(2-hydroxyethyl)acetamide, ... (5 entities in total)
• Functional Keywords: alpha-beta complex, adp-ribosyl transferase, nad+ binding, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Vibrio cholerae
• Total number of polymer chains: 1
• Total formula weight: 23927.40

Authors

Merrill, A.R.,Jorgensen, R. (deposition date: 2010-07-14, release date: 2010-12-29, Last modification date: 2023-09-06)

Primary citation

Turgeon, Z.,Jorgensen, R.,Visschedyk, D.,Edwards, P.R.,Legree, S.,McGregor, C.,Fieldhouse, R.J.,Mangroo, D.,Schapira, M.,Merrill, A.R.
Newly discovered and characterized antivirulence compounds inhibit bacterial mono-ADP-ribosyltransferase toxins.
Antimicrob.Agents Chemother., 55:983-991, 2011

PubMed Abstract: The mono-ADP-ribosyltransferase toxins are bacterial virulence factors that contribute to many disease states in plants, animals, and humans. These toxins function as enzymes that target various host proteins and covalently attach an ADP-ribose moiety that alters target protein function. We tested compounds from a virtual screen of commercially available compounds combined with a directed poly(ADP-ribose) polymerase (PARP) inhibitor library and found several compounds that bind tightly and inhibit toxins from Pseudomonas aeruginosa and Vibrio cholerae. The most efficacious compounds completely protected human lung epithelial cells against the cytotoxicity of these bacterial virulence factors. Moreover, we determined high-resolution crystal structures of the best inhibitors in complex with cholix toxin to reveal important criteria for inhibitor binding and mechanism of action. These results provide new insight into development of antivirulence compounds for treating many bacterial diseases.

PubMed: 21135177
DOI: 10.1128/AAC.01164-10

Experimental method

X-RAY DIFFRACTION (1.68 Å)