The Mode of Action and the Structure of a Herbicide in Complex with its Target: Binding of Activated Hydantocidin to the Feedback Regulation Site of Adenylosuccinate Synthetase

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 18; pp. 9431 - 9436
• Main Authors: Fonné-Pfister, R., Chemla, P., Ward, E., Girardet, M., Kreuz, K. E., Honzatko, R. B., Fromm, H. J., H.-P. Schär, Grütter, M. G., Cowan-Jacob, S. W.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 03.09.1996; National Acad Sciences
• Subjects: Adenylosuccinate Synthase - metabolism; Amino Acid Sequence; Atoms; Basil; Binding Sites; Biochemistry; Cell growth; Cells, Cultured; Crystallography, X-Ray; DNA, Complementary - analysis; Enzymes; Escherichia coli; Feedback; Herbicides; Herbicides - chemistry; Herbicides - metabolism; Hydantoins - chemistry; Hydantoins - metabolism; Inhibitory concentration 50; Molecular Sequence Data; Molecules; Phenotype; Plants; Protein Conformation; Sequence Homology, Amino Acid; Tetrahedrons
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.18.9431

(+)-Hydantocidin, a recently discovered natural spironucleoside with potent herbicidal activity, is shown to be a proherbicide that, after phosphorylation at the 5′ position, inhibits adenylosuccinate synthetase, an enzyme involved in de novo purine synthesis. The mode of binding of hydantocidin 5′-monophosphate to the target enzyme was analyzed by determining the crystal structure of the enzyme-inhibitor complex at 2.6- angstrom resolution. It was found that adenylosuccinate synthetase binds the phosphorylated compound in the same fashion as it does adenosine 5′-monophosphate, the natural feedback regulator of this enzyme. This work provides the first crystal structure of a herbicide-target complex reported to date.