• Publications
  • Influence
Modeling of the spatial structure of eukaryotic ornithine decarboxylases
TLDR
A topographic model of the pyridoxal phosphate‐binding domain of ornithine decarboxylase is developed, which predicts that the Schiff base lysine and a conserved glycine‐rich sequence both map to the C‐termini of the β‐strands. Expand
Yeast dihydroorotate dehydrogenase as a new selectable marker for Plasmodium falciparum transfection.
TLDR
This work has successfully disrupted the type II vacuolar proton-pumping pyrophosphatase gene in P. falciparum by double crossover recombination, showing that this gene is not essential for the survival of blood stage parasites. Expand
Plasmodium dihydroorotate dehydrogenase: a promising target for novel anti-malarial chemotherapy.
TLDR
Recent studies to exploit the fourth enzyme in the de novo pyrimidine biosynthetic pathway of P. falciparum, dihydroorotate dehydrogenase, as a new target for drug discovery provide strong evidence that PfDHODH is a validated target for the identification of new antimalarial chemotherapy. Expand
Chemical genetics of Plasmodium falciparum
TLDR
A phenotypic forward chemical genetic approach to discover new antimalarial chemotypes and structures and biological activity of the entire library are disclosed, many of which showed potent in vitro activity against drug-resistant P. falciparum strains. Expand
A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria
TLDR
The excellent safety profile, blood- and liver-stage activity, and predicted long half-life in humans position DSM265 as a new potential drug combination partner for either single-dose treatment or once-weekly chemoprevention of malaria. Expand
Malarial Dihydroorotate Dehydrogenase
TLDR
Direct evidence is provided that the malarial DHODH active site is different from the host enzyme, and that it is an attractive target for the development of new anti-malarial agents. Expand
X-ray structure of ornithine decarboxylase from Trypanosoma brucei: the native structure and the structure in complex with alpha-difluoromethylornithine.
TLDR
The structure offers insight into the enzyme mechanism by providing details of the enzyme/inhibitor binding site and allows for a detailed comparison between the enzymes from the host and parasite which will aid in selective inhibitor design. Expand
An Alternative Polyamine Biosynthetic Pathway Is Widespread in Bacteria and Essential for Biofilm Formation in Vibrio cholerae*
TLDR
In vivo characterization of an alternative polyamine biosynthetic pathway from Vibrio cholerae, the causative agent of human cholera, is reported, likely to play a previously unrecognized role in the biology of these organisms. Expand
High-throughput Screening for Potent and Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase*
TLDR
The structural basis for the species selective enzyme inhibition is explained by the variable amino acid sequence in this binding site, making DHODH a particularly strong candidate for the development of new anti-malarial compounds. Expand
Crystal structure of human ornithine decarboxylase at 2.1 A resolution: structural insights to antizyme binding.
TLDR
Analysis of the solvent-accessible surface area, surface electrostatic potential, and the conservation of primary sequence between human and Trypanosoma brucei ODC provides clues to the identity of potential protein-binding-determinants in the putative antizyme binding element in human ODC. Expand
...
1
2
3
4
5
...