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The E. coli argE-encoded N-acetyl-L-ornithine deacetylase has been cloned, expressed, and purified in high yield. The substrate specificity of the enzyme is relatively broad, with a number of alpha-N-acyl-L-amino acids exhibiting activity, including both alpha-N-acetyl- and alpha-N-formylmethionine that exhibit higher activity than(More)
The inhA gene has been recently shown to encode a common protein target for isoniazid and ethionamide action in Mycobacterium tuberculosis. In this paper, we demonstrate that the M. tuberculosis InhA protein catalyzes the NADH-specific reduction of 2-trans-enoyl-ACP, essential for fatty acid elongation. This enzyme preferentially reduces long-chain(More)
Resistance to isoniazid in Mycobacterium tuberculosis can be mediated by substitution of alanine for serine 94 in the InhA protein, the drug's primary target. InhA was shown to catalyze the beta-nicotinamide adenine dinucleotide (NADH)-specific reduction of 2-trans-enoyl-acyl carrier protein, an essential step in fatty acid elongation. Kinetic analyses(More)
A number of quinones were analyzed as substrates for trypanothione reductase from Trypanosoma congolense, an enzyme responsible for the protection of trypanosomes against oxidative stress. Using NADPH as substrate, the maximal rate of the steady-state reaction at pH 7.5 was between 24 and 1.6 s-1 for 11 quinone substrates. The biomolecular steady-state rate(More)
Fluoroquinolones are gaining increasing importance in the treatment of tuberculosis. The expression of MfpA, a member of the pentapeptide repeat family of proteins from Mycobacterium tuberculosis, causes resistance to ciprofloxacin and sparfloxacin. This protein binds to DNA gyrase and inhibits its activity. Its three-dimensional structure reveals a fold,(More)
L-Phenylalanine dehydrogenase catalyzes the NAD(+)-dependent, reversible, oxidative deamination of L-phenylalanine to form ammonia, phenyl pyruvate, and NADH. The enzyme has been purified to homogeneity from Rhodococcus sp. M4, and a partial amino acid sequence was obtained. A cosmid library of Rhodococcus sp. M4 genomic DNA was prepared and used to isolate(More)
beta-lactam antibiotics are ineffective against Mycobacterium tuberculosis, being rapidly hydrolyzed by the chromosomally encoded blaC gene product. The carbapenem class of beta-lactams are very poor substrates for BlaC, allowing us to determine the three-dimensional structure of the covalent BlaC-meropenem covalent complex at 1.8 angstrom resolution. When(More)
The first unique step in bacterial and plant methionine biosynthesis involves the acylation of the gamma-hydroxyl of homoserine. In Haemophilus influenzae, acylation is accomplished via an acetyl-CoA-dependent acetylation catalyzed by homoserine transacetylase. The activity of this enzyme regulates flux of homoserine into multiple biosynthetic pathways and,(More)
Nitrofurans with aromatic and heterocyclic substituents inhibit Trypanosoma congolense trypanothione reductase (TR) and yeast glutathione reductase (GR), acting as uncompetitive inhibitors vs. NADPH and noncompetitive or uncompetitive inhibitors vs. disulfide substrate. Many of these compounds inhibited trypanothione reductase more efficiently than(More)