Fonné-Pfister R, Chemla P, Ward E, Girardet M, Kreuz K E, Honzatko R B, Fromm H J, Schär H P, Grütter M G, Cowan-Jacob S W
Pharmaceutical Division, Ciba-Geigy Ltd., Basel, Switzerland.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9431-6. 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-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.
（+）-杀稻瘟菌素是最近发现的一种具有强大除草活性的天然螺核苷，它被证明是一种前除草剂，在5'位磷酸化后，可抑制参与嘌呤从头合成的腺苷酸琥珀酸合成酶。通过测定酶-抑制剂复合物在2.6埃分辨率下的晶体结构，分析了杀稻瘟菌素5'-单磷酸与靶酶的结合模式。发现腺苷酸琥珀酸合成酶以与该酶的天然反馈调节剂腺苷5'-单磷酸相同的方式结合磷酸化化合物。这项工作提供了迄今为止报道的第一个除草剂-靶标复合物的晶体结构。
