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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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The Interaction of Barley Acetolactate Synthase with 4,6-Dimethoxypyrimidine Inhibitors

  • Shim, Hee-Ok (Department of Biochemistry, Chungbuk National University) ;
  • Kim, Dae-Whang (Korea Research Institute of Chemical Technology) ;
  • Chang, Soo-Ik (Department of Biochemistry, Chungbuk National University) ;
  • Choi, Jung-Do (Department of Biochemistry, Chungbuk National University)
  • Received : 1995.06.19
  • Published : 1995.11.30
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Abstract

Acetolactate synthase (ALS) catalyzes the first common step in the biosynthesis of valine, leucine, and isoleucine. ALS is the target enzyme for several classes of structually diverse herbicides. We have synthesized 4,6-dimethoxypyrimidine derivatives as ALS inhibitors, and their inhibitory activities on barley ALS were determined. $IC_{50}$ values for the derivatives are 0.2~200 ${\mu}m$. K11570, the most potent ALS inhibitor with $IC_{50}$ of 0.2 ${\mu}m$, showed mixed-type inhibition with respect to substrate pyruvate, and the progress curves for ALS inhibition by K11570 indicated that the amount of inhibition increased with time. Inhibition-competition experiments were carried out and indicated that three different classes of inhibitors, K11570, a sulfonylurea Ally, and leucine, bind to ALS in a mutually exclusive manner. Chemical modification of tryptophanyl and tyrosyl residues of ALS decreased the sensitivity of ALS to K11570, while cysteine modification did not affect the sensitivity. These results suggest that tryptophanyl and tyrosynyl residues are probably located at or near the inhibitor binding site.

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