Orotidine Monophosphate Decarboxylase——A Fascinating Workhorse Enzyme with Therapeutic Potential

Orotidine 50-monophosphate decarboxylase(ODCase) is known as one of the most proficient enzymes. The enzyme catalyzes the last reaction step of the de novo pyrimidine biosynthesis, the conversion from orotidine 50-monophosphate(OMP) to uridine 50-monophosphate. The enzyme is found in all three domains of life, Bacteria, Eukarya and Archaea. Multiple sequence alignment of 750 putative ODCase sequences resulted in five distinct groups. While the universally conserved Dx Kxx Dx motif is present in all the groups,depending on the groups, several characteristic motifs and residues can be identified. Over 200 crystal structures of ODCases have been determined so far. The structures, together with biochemical assays and computational studies, elucidated that ODCase utilized both transition state stabilization and substrate distortion to accelerate the decarboxylation of its natural substrate. Stabilization of the vinyl anion intermediate by a conserved lysine residue at the catalytic site is considered the largest contributing factor to catalysis, while bending of the carboxyl group from the plane of the aromatic pyrimidine ring of OMP accounts for substrate distortion. A number of crystal structures of ODCases complexed with potential drug candidate molecules have also been determined, including with 6-iodouridine, a potential antimalarial agent.     

Mutagenicity of N-hydroxylamines and N-hydroxycarbamates towards strains of Escherichia coli and Salmonella typhimurium

The mutagenic activity of several arylamines, alkyl- and arylcarbamates and their corresponding N-hydroxylated derivatives towards Escherichia coli WP2uvrA was investigated using the fluctuation test without a metabolic activation system. None of the parent amines or carbamates were mutagenic while several arylhydroxylamines and N-hydroxycarbamates were direct-acting base-pair substitution mutagens. With the exception of n-hexyl-N-hydroxycarbamate, the mutagenic activity of the N-hydroxycarbamates increased with increase in the length of alkyl substituent. Some arylamines and arylhydroxylamines were further examined, again without a metabolic activation system, using a plate test in conjunction with bacterial strains which detect either base-pair or frameshift mutagens. The arylhydroxylamines were found to cause both base-pair and frameshift mutations but were more active as frameshift mutagens. Possible reasons for the observed mutagenic activity are considered.     

Diphyllobothrium latum infection after eating domestic salmon flesh.

Diphyllobothrium latum infection in human is not common in Korea and only thirty seven cases have been reported since 1921. We report two cases of fish tapeworm infection after ingestion of raw cherry salmon (Oncorhynchus masou) caught in the domestic river. Among four family members who ate together raw salmon flesh six months ago, just two, mother and daughter, were infected. It is our expectation that the salmon associated tapeworm infections would be enlisted as one of the major parasitic problems with the growing consumption of salmon in Korea.     

Molecular Mapping and Character Tagging in Mustard (Brassica juncea) II. Association of RFLP markers with Seed Coat Colour and Quantitative Traits

In Brassica juncea, segregation of 44 RFLP markers generated by homologous genomic DNA clones as probes was studied in a F₂ population obtained from an intervarietal cross. Linkage relationship among the markers was established using computer package ‘MAPMAKER’. Twenty five of the markers could be arranged in nine linkage groups, covering a total of 243.3 cM. Marker BJG357c showed tight linkage (3.9 cM) with yellow seed coat colour locus (r ₁). Based on single factor analysis of variance,17 significant marker-trait associations could be established in respect of six quantitative traits viz. days to flowering, plant height, number of primary branches, secondary branches per primary branch, siliquea per secondary branch, and seeds per siliqua. The proportion of phenotypic variation explained by individual marker-trait association ranged from 3.0% to 33.2%. The putative gene action at majority of the marked genomic regions was found to be partial dominance to dominance.