This laboratory uses mutants in the yeast Saccharomyces cerevisiae, and in the bacterium, Escherichia coli, to study the biochemical genetics of glycolysis, and important pathway in most cells. The present application is mainly for the following projects. (i) To clarify gene enzyme relationships in yeast phosphofructokinase, an enzyme with non-identical subunits which, possibly, are catalytic and regulatory, respectively. (ii) To pursue a study of the newly recognized controlling metabolite, fructose-2, 6-P2, in yeast, with the particular aim of obtaining mutants lacking it, in order to probe its synthesis and function. And (iii), to investigate the biochemical genetics of fructose bisphosphatase, in order to help clarify the roles of three mechanisms known to govern its activity in yeast - inhibition by effectors, repression, and catabolite inactivation - as well as to study the same reaction in E. coli.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021098-14
Application #
3270247
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1977-08-01
Project End
1988-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
14
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Behlke, J; Heidrich, K; Naumann, M et al. (1998) Hexokinase 2 from Saccharomyces cerevisiae: regulation of oligomeric structure by in vivo phosphorylation at serine-14. Biochemistry 37:11989-95
Uemura, H; Jigami, Y (1992) GCR3 encodes an acidic protein that is required for expression of glycolytic genes in Saccharomyces cerevisiae. J Bacteriol 174:5526-32
Paravicini, G; Kretschmer, M (1992) The yeast FBP26 gene codes for a fructose-2,6-bisphosphatase. Biochemistry 31:7126-33
Kretschmer, M; Tempst, P; Fraenkel, D G (1991) Identification and cloning of yeast phosphofructokinase 2. Eur J Biochem 197:367-72
Kretschmer, M; Fraenkel, D G (1991) Yeast 6-phosphofructo-2-kinase: sequence and mutant. Biochemistry 30:10663-72
Vojtek, A B; Fraenkel, D G (1990) Phosphorylation of yeast hexokinases. Eur J Biochem 190:371-5
Uemura, H; Fraenkel, D G (1990) gcr2, a new mutation affecting glycolytic gene expression in Saccharomyces cerevisiae. Mol Cell Biol 10:6389-96
Babul, J; Fraenkel, D G (1988) Phosphate modification of fructose-1,6-bisphosphate aldolase in Escherichia coli. Biochem Biophys Res Commun 151:1033-8
Sedivy, J M; Babul, J; Fraenkel, D G (1986) AMP-insensitive fructose bisphosphatase in Escherichia coli and its consequences. Proc Natl Acad Sci U S A 83:1656-9
Baker, H V (1986) Glycolytic gene expression in Saccharomyces cerevisiae: nucleotide sequence of GCR1, null mutants, and evidence for expression. Mol Cell Biol 6:3774-84

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