Synthesis, crystal structure and biological evaluation of substituted quinazolinone benzoates as novel antituberculosis agents targeting acetohydroxyacid synthase.

Acetohydroxyacid synthase (AHAS) catalyzes the first essential biosynthetic step of branched-chain amino acids and is a biologically safe target against Mycobacterium tuberculosis (MTB). In our previous research, we used virtual screening to identify some novel AHAS inhibitors as potent antituberculosis agents. In this study, we synthesized twenty-four additional quinazolinone benzoates and explored their antitubercular activity.

Mutational analysis of critical residues of FAD-independent catabolic acetolactate synthase from Enterococcus faecalis V583.

Catabolic acetolactate synthase (cALS) from Enterococcus faecalis is a FAD-independent enzyme, which catalyzes the condensation of two molecules of pyruvate to produce acetolactate. Mutational and kinetic analyses of variants suggested the importance of H111, Q112, and Q411 residues for catalysis in cALS. The wild-type and variants were expressed as equally soluble proteins and co-migrated to a size of 60 kDa on SDS-PAGE.

Development of ssDNA aptamers for the sensitive detection of Salmonella typhimurium and Salmonella enteritidis.

Salmonella enterica subsp. enterica ser. enteritidis and Salmonella enterica subsp.

Structural and functional significance of the highly-conserved residues in Mycobacterium tuberculosis acetohydroxyacid synthase.

Mycobacterium tuberculosis AHAS is a potential target for the development of novel anti-tuberculosis agents. Silico analysis showed that conserved His84 and Gln86 residues lie in the catalytic dimer interface of M. tuberculosis AHAS.

Role of a highly conserved proline-126 in ThDP binding of Mycobacterium tuberculosis acetohydroxyacid synthase.

Acetohydroxyacid synthase (AHAS) of Mycobacterium tuberculosis is a promising target for the development of anti-tuberculosis agents. With the absence of an available bacterial AHAS crystal structure, that of M. tuberculosis, site-directed mutagenesis has been a useful tool for determining its structural and functional features.

Biochemical characterization and evaluation of potent inhibitors of the Pseudomonas aeruginosa PA01 acetohydroxyacid synthase.

Microbes and plants synthesize essential branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine via a common biosynthetic pathway in which the first reaction is catalyzed by acetohydroxyacid synthase (AHAS, EC 4.1.3.