Mecanismo, estructura e inhibición de la enzima Acetohidroxiácido Sintasa

Abstract

The Acetohydroxy acid ctase (AHAS, E.C. 2.2.1.6) or acetolactate withouttase (ALS), is an enzyme dependent on thiamine diphosphate (ThDP) which is present in plants and microorganism. It participates in branched-chain amino acid biosynthesis BCAAs. In the presence of ThDP, FAD and a divalent metallic, it comprises the condensation of two pyruvate molecules into 2-acetolatate or a pyruvate molecule or one of 2-cetobutirate into 2-acete-2-hydroxybutyrate to form the valine, leucine and isoleucine. Structurally, four catalytic subunits (CSUs) interact with four (plant) or eight (yeast) regulatory subunits RSUs forming the enzyme complex AHAS. CSU owns the active site, while RSU increases the CSU activity and provides enzymatic sensitivity to feedback inhibition. Its inhibition has a biocidal effect, which occurs through different reactions and molecular interactions, where the best known is produced by molecules with herbicidal activity, making the enzyme an important target for the development of more than 58 herbicides. In recent years, research has focused on using AHAS inhibitor herbicides as antimicrobials, taking advantage of the absence of the enzyme in humans. Also, mutations and new inhibitors are being studied with promising results. Therefore, this study proposes to consolidate the available literature about the structure, function, and inhibition of AHAS to contribute to future projects by defining research needs in this area and the prospects for the use of the enzyme or its inhibitors in medical, biotechnological, bioinformatics, other applications.