Gedi, Vinayakumar Jayaraman, Kumaresan Kalme, Satish Park, Hye-Yeon Park, Hae-Chul La, Im-Joung Hahn, Hoh-Gyu Yoon, Moon-Young 2024-01-20T19:04:22Z 2024-01-20T19:04:22Z 2021-09-02 2010-06 1570-9639 https://pubs.kist.re.kr/handle/201004/131404 Acetohydroxyacid synthase (AHAS), a potential target for antimicrobial agents, catalyzes the first common step in the biosynthesis of the branched-chain amino acids. The genes of both catalytic and regulatory subunits of AHAS from Bacillus anthracis (Bantx), a causative agent of anthrax, were cloned, overexpressed in Escherichia coli, and purified to homogeneity. To develop novel anti-anthracis drugs that inhibit AHAS, a chemical library was screened, and four chemicals, AVS2087, AVS2093, AVS2387, and AVS2236, were identified as potent inhibitors of catalytic subunit with IC50 values of 1.0 +/- 0.02, 1.0 +/- 0.04, 2.1 +/- 0.12, and 2.0 +/- 0.08 mu M, respectively. Further, these four chemicals also showed strong inhibition against reconstituted AHAS with IC50 values of 0.05 +/- 0.002, 0.153 +/- 0.004, 1.30 +/- 0.10, and 1.29 +/- 0.40 mu M, respectively. The basic scaffold of the AVS group consists of 1-pyrimidine-2-yl-1H-[1,2,4]triazole-3-sulfonamide. The potent inhibitor, AVS2093 showed the lowest binding energy, -8.52 kcal/mol and formed a single hydrogen bond with a distance of 1.973. As the need for novel antibiotic classes to combat bacterial drug resistance increases, the screening of new compounds that act against Bantx-AHAS shows that AHAS is a good target for new anti-anthracis drugs. (C) 2010 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV ESCHERICHIA-COLI BIOSYNTHETIC-PATHWAY POTENT INHIBITORS AMINO-ACIDS SUBUNITS IDENTIFICATION RECONSTITUTION TUBERCULOSIS ACETOLACTATE BINDING Evaluation of substituted triazol-1-yl-pyrimidines as inhibitors of Bacillus anthracis acetohydroxyacid synthase Article 10.1016/j.bbapap.2010.02.002 1 BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v.1804, no.6, pp.1369 - 1375 BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 1804 6 1369 1375 scie scopus 000277219300013 2-s2.0-77949914910 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article ESCHERICHIA-COLI BIOSYNTHETIC-PATHWAY POTENT INHIBITORS AMINO-ACIDS SUBUNITS IDENTIFICATION RECONSTITUTION TUBERCULOSIS ACETOLACTATE BINDING Acetohydroxyacid synthase Bacillus anthracis Docking Reconstitution Triazol-1-yl-pyrimidines