Antimycobacterially active salicylanilide diethyl phosphates were evaluated to identify their potential drug target(s) for the inhibition of several mycobacterial enzymes, including isocitrate lyase, L-alanine dehydrogenase (MtAlaDH), lysine ε-aminotransferase, chorismate mutase, and pantothenate synthetase. The enzymes are related to the nongrowing state of Mycobacterium tuberculosis. Salicyla...

Following a previous report on physicochemical properties, the enzymological properties of a homogeneously purified preparation of pantothenate synthetase were described. The optimum pH was 10.0 and optimum temperature 30 degrees C. The lyophilized enzyme was very stable on standing at -20 degrees C. K+ or NH4+ and Mg2+ were required as activators; other cations examined were inhibitive to vari...

The inhibition rate of L(-)pantothenate as an antagonist of D(+)pantothenate was discussed from the viewpoint of growth and lipid metabolism. The growth rate of mice given pantothenate-deficient diets containing L(-)pantothenate (300 mg per 100g diet) was markedly decreased, and such pantothenate-deficient symptoms as "spectacle eyes" appeared. However, it was recovered by the simultaneous addi...

Tuberculosis (TB) is a global health burden especially in tropical countries. Extensive increments MDR (Multidrug resistance (MDR): Resistance to at least both isoniazid and rifampicin.) XDR (Extensive drug (XDR): any fluoroquinolone, one of three second-line injectable drugs (capreomycin, kanamycin, amikacin), addition multidrug resistance) tuberculosis highlights the ineffectiveness establish...

Although bacteria and eukaryotes share a pathway for coenzyme A (CoA) biosynthesis, we previously clarified that most archaea utilize a distinct pathway for the conversion of pantoate to 4'-phosphopantothenate. Whereas bacteria/eukaryotes use pantothenate synthetase and pantothenate kinase (PanK), the hyperthermophilic archaeon Thermococcus kodakarensis utilizes two novel enzymes: pantoate kina...

Pyrazinamide (PZA) is a first-line tuberculosis drug that inhibits the growth of Mycobacterium tuberculosis via an as yet undefined mechanism. An M. tuberculosis laboratory strain that was auxotrophic for pantothenate was found to be insensitive to PZA and to the active form, pyrazinoic acid (POA). To determine whether this phenotype was strain or condition specific, the effect of pantothenate ...

Pantothenate, the precursor of coenzyme A, is an essential nutrient for the intraerythrocytic stage of the malaria parasite Plasmodium falciparum. Pantothenate enters the malaria-infected erythrocyte via new permeation pathways induced by the parasite in the host cell membrane (Saliba, K. J., Horner, H. A., and Kirk, K. (1998) J. Biol. Chem. 273, 10190–10195). We show here that pantothenate is ...

Pantothenate biosynthesis is essential for the virulence of Mycobacterium tuberculosis, and this pathway thus presents potential drug targets against tuberculosis. We determined the crystal structure of pantothenate synthetase (PS) from M. tuberculosis, and its complexes with AMPCPP, pantoate, and a reaction intermediate, pantoyl adenylate, with resolutions from 1.6 to 2 A. PS catalyzes the ATP...

fluid, and Tables 3 and 6 that the glycolysis of suspensions is unaffected by the compound. A small stimulation only was fotmd in previous experiments with the same organism (McIlwain, 1944) in which, in contrast with the present work, the course of glycolysis was measured. Pantothenate is always present in small quantities in the organisms; nevertheless, if free pantothenate is present, it is ...