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. |
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Authors: | R Fonné-Pfister P Chemla E Ward M Girardet K E Kreuz R B Honzatko H J Fromm H P Sch?r M G Grütter S W Cowan-Jacob |
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Affiliation: | Pharmaceutical Division, Ciba-Geigy Ltd., Basel, Switzerland. |
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Abstract: | (+)-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-A 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. |
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