Wang Jian-Guo, Lee Patrick K-M, Dong Yu-Hui, Pang Siew Siew, Duggleby Ronald G, Li Zheng-Ming, Guddat Luke W
State Key Laboratory of Elemento-Organic Chemistry, National Pesticide Engineering Research Center, Nankai University, Tianjin, China.
FEBS J. 2009 Mar;276(5):1282-90. doi: 10.1111/j.1742-4658.2009.06863.x.
Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) is the first enzyme in the biosynthetic pathway of the branched-chain amino acids. It catalyzes the conversion of two molecules of pyruvate into 2-acetolactate or one molecule of pyruvate and one molecule of 2-ketobutyrate into 2-aceto-2-hydroxybutyrate. AHAS requires the cofactors thiamine diphosphate (ThDP), Mg(2+) and FAD for activity. The herbicides that target this enzyme are effective in protecting a broad range of crops from weed species. However, resistance in the field is now a serious problem worldwide. To address this, two new sulfonylureas, monosulfuron and monosulfuron ester, have been developed as commercial herbicides in China. These molecules differ from the traditional sulfonylureas in that the heterocyclic ring attached to the nitrogen atom of the sulfonylurea bridge is monosubstituted rather than disubstituted. The structures of these compounds in complex with the catalytic subunit of Arabidopsis thaliana AHAS have been determined to 3.0 and 2.8 A, respectively. In both complexes, these molecules are bound in the tunnel leading to the active site, such that the sole substituent of the heterocyclic ring is buried deepest and oriented towards the ThDP. Unlike the structures of Arabidopsis thaliana AHAS in complex with the classic disubstituted sulfonylureas, where ThDP is broken, this cofactor is intact and present most likely as the hydroxylethyl intermediate.
乙酰羟酸合酶（AHAS；EC 2.2.1.6）是支链氨基酸生物合成途径中的第一种酶。它催化两分子丙酮酸转化为2-乙酰乳酸，或一分子丙酮酸和一分子2-酮丁酸转化为2-乙酰-2-羟基丁酸。AHAS需要硫胺素二磷酸（ThDP）、Mg(2+)和FAD作为辅因子来发挥活性。靶向该酶的除草剂能有效保护多种作物免受杂草侵害。然而，田间抗性现在是一个全球性的严重问题。为了解决这个问题，在中国已开发出两种新型磺酰脲类除草剂，单嘧磺隆和单嘧磺隆酯。这些分子与传统磺酰脲类的不同之处在于，连接在磺酰脲桥氮原子上的杂环是单取代而非双取代。已分别确定这些化合物与拟南芥AHAS催化亚基形成复合物时的结构，分辨率为3.0 Å和2.8 Å。在这两种复合物中，这些分子都结合在通向活性位点的通道中，使得杂环的唯一取代基埋得最深且朝向ThDP。与拟南芥AHAS与经典双取代磺酰脲类形成复合物的结构不同，在后者中ThDP被破坏，而在这些复合物中，该辅因子是完整的，很可能以羟乙基中间体的形式存在。
