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Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs.
A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria and the presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprene biosynthesis in P. falcIParum depends on the DOXP pathway. Expand
Antimicrobial peptides: The ancient arm of the human immune system
Clinical studies on the treatment of infectious diseases have been performed with artificial peptides derived from human lactoferrin, histatins and BPI in addition to porcine protegrins, frog magains and bovine indolicidin, showing increasing evidence that AMPs play a crucial role in human immunity. Expand
Identification of (E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl pyrophosphate as a major activator for human γδ T cells in Escherichia coli
The gcpE and lytB gene products control the terminal steps of isoprenoid biosynthesis via the 2‐C‐methyl‐D‐erythritol 4‐phosphate pathway in Escherichia coli. In lytB‐deficient mutants, a highlyExpand
Microbial isoprenoid biosynthesis and human γδ T cell activation
Unexpectedly, the intermediate of the MEP pathway, (E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl‐pyrophosphate) (HMB‐PP), turned out to be by far the most potent Vγ9/Vδ2 T cell activator known, with an EC50 of 0.1 nM. Expand
LytB protein catalyzes the terminal step of the 2‐C‐methyl‐D‐erythritol‐4‐phosphate pathway of isoprenoid biosynthesis
Recombinant LytB protein from the thermophilic eubacterium Aquifex aeolicus produced in Escherichia coli was purified to apparent homogeneity and catalyzed the reduction of (E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl diphosphate in a defined in vitro system. Expand
Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human gammadelta T cells in Escherichia coli.
This compound was purified from E. coli DeltalytB mutants by preparative anion exchange chromatography, and identified by mass spectrometry, (1)H, (13)C and (31)P NMR spectroscopy, and NOESY analysis as HMB-PP, which is 10(4) times more potent in activating human Vgamma9/Vdelta2 T cells than isopentenyl pyrophosphate. Expand
New antimalarial drugs.
New data available from the recently sequenced genome of the malaria parasite Plasmodium falciparum and the application of methods of modern drug design promise to bring significant development in the fight against this disease. Expand
Differential Stimulation of the Na+/H+ Exchanger Determines Chloroquine Uptake in Plasmodium falciparum
Here we describe the identification and characterization of a physiological marker that is associated with the chloroquine-resistant (CQR) phenotype in the human malarial parasite PlasmodiumExpand
Inhibition of the Non-Mevalonate 1-Deoxy-ᴅ-xylulose-5-phosphate Pathway of Plant Isoprenoid Biosynthesis by Fosmidomycin
Abstract Various bacterial and plastidic plant terpenoids are synthesized via the non-mevalonate1-deoxy-ᴅ-xylulose-5-phosphate (DOXP) pathway. The antibiotic and herbicidal compound fosmidomycin isExpand
RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA.
This study represents the first in vitro description of a methyl transfer catalyzed by a member of the Radical SAM superfamily, and it expands the catalytic repertoire of this diverse enzyme class. Expand