The structure, function and catalytic properties of the cytoplasmic and mitochondrial forms of the trifunctional enzyme C1-tetrahydrofolate synthase from yeast, and of the corresponding monofunctional and bifunctional enzymes that occur in non-eukaryotic cells will be examined. The yeast enzymes are products of the ADE3 and MIS1 genes respectively. These enzymes catalyze the interconversion of three coenzyme forms of folic acid, a vitamin required by humans for the synthesis and metabolism of proteins and amino acids, nucleic acids and purines and pyrimidines, and a vitamin. The structure of the crystalline Clostridium acidi-urici 10- formyl-tetrahydrofolate synthetase, one of the component enzymes of the yeast trifunctional enzyme, will be determined from the crystals of that enzyme. We will attempt to crystallize the yeast trifunctional form of the enzyme, as well as the mono- and bifunctional enzymes that occur in other cells for purposes of structural comparisons and correlation of the structural features with the differences in their activities and functions. The catalytic functions of both trifunctional enzymes in the synthesis of purine bases has been questioned. It has been proposed that the ADE3 gene functions as a matrix for the enzyme complex involved in purine base biosynthesis. We will attempt to determine what the physiological function of each enzyme is in the cell.
| Song, J M; Cheung, E; Rabinowitz, J C (1996) Organization and characterization of the two yeast ribosomal protein YL19 genes. Curr Genet 30:273-8 |
| Song, J M; Cheung, E; Rabinowitz, J C (1995) Nucleotide sequence and characterization of the Saccharomyces cerevisiae RPL19A gene encoding a homolog of the mammalian ribosomal protein L19. Yeast 11:383-9 |
| Song, J M; Rabinowitz, J C (1995) The N-terminal, dehydrogenase/cyclohydrolase domain of yeast cytoplasmic trifunctional C1-tetrahydrofolate synthase requires the C-terminal, synthetase domain for the catalytic activity in vitro. FEBS Lett 376:229-32 |
