Many virtual screening methods have been developed for identifying single-target inhibitors based on the strategy of "one-disease, one-target, one-drug". The hit rates of these methods are often low because they cannot capture the features that play key roles in the biological functions of the target protein. Furthermore, single-target inhibitors are often susceptible to drug resistance and are...

Poplar (Populus tremula x alba) trees (clone INRA 717-1-B4) were cultivated for 1 month in phytotronic chambers with two different levels of ozone (60 and 120 nL L(-1)). Foliar activities of shikimate dehydrogenase (EC 1.1.1.25), phenylalanine ammonia lyase (EC 4.3.1.5), and cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195) were compared with control levels. In addition, we examined lignin con...

The shikimic acid biosynthetic pathway, which operates in micro-organisms and higher plants but not in mammals, leads to several essential amino acids and also to a variety of other metabolites. It was hoped, therefore, that blockage of the pathway might have a damaging effect on plant metabolism, giving a useful commercial herbicide with selective toxicity. Shikimate dehydrogenase, the enzyme ...

Shikimate kinase II was purified to near homogeneity from an Escherichia coli strain which overproduced the enzyme. The apparent Km of this isoenzyme for shikimate was 200 microM, and for ATP it was 160 microM. The Km for shikimate is approximately 100-fold lower than the Km of shikimate kinase I, suggesting that shikimate kinase II is the isoenzyme normally functioning in aromatic biosynthesis...

The apicomplexan parasite Toxoplasma gondii, the etiologic agent of toxoplasmosis, is estimated to infect 10-80% of different human populations. T. gondii encodes a large pentafunctional polypeptide known as the AROM complex which catalyzes five reactions in the shikimate pathway, a metabolic pathway required for the biosynthesis of the aromatic amino acids and a promising target for anti-paras...

The conversion of prephenic acid to tyrosine can occur by two different routes: (a) oxidative decarboxylation (prephenate dehydrogenase) followed by transamination (aromatic aminotransferase); (b) transamination of prephenate forming the non-aromatic amino acid arogenic acid (prephenate aminotransferase) followed by oxidative decarboxylation (arogenate dehydrogenase). High activity of arogenate...