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

(+)-Hydantocidin, a recently discovered natural spironucleoside with p otent herbicidal activity, is shown to be a proherbicide that, after p hosphorylation at the 5' position, inhibits adenylosuccinate synthetas e, 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 aden osine 5'-monophosphate, the natural feedback regulator of this enzyme. This work provides the first crystal structure of a herbicide-target complex reported to date.