Cellular processes are ultimately regulated by proteins and enzymes. The control of the key enzymes of many cellular processes is by allosteric regulation which may be coupled of phosphorylation - a covalent post translation switch that changes protein function. Glycogen metabolism is the most basic process for regulating energy stores of cells and is controlled by glycogen phosphorylase. Using X-ray crystallography, the three dimensional structures of glycogen phosphorylases from muscle, liver, brain and yeast cells will be defined. The structure role of the covalent phosphorylation of these enzymes and its relationship role to the allosteric regulation by small molecule ligands will be determined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK026081-12
Application #
3227720
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1979-07-01
Project End
1994-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
12
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Rath, V L; Fletterick, R J (1994) Parallel evolution in two homologues of phosphorylase. Nat Struct Biol 1:681-90
Luong, C B; Browner, M F; Fletterick, R J et al. (1992) Purification of glycogen phosphorylase isozymes by metal-affinity chromatography. J Chromatogr 584:77-84
Rath, V L; Hwang, P K; Fletterick, R J (1992) Purification and crystallization of glycogen phosphorylase from Saccharomyces cerevisiae. J Mol Biol 225:1027-34
Browner, M F; Hwang, P K; Fletterick, R J (1992) Cooperative binding is not required for activation of muscle phosphorylase. Biochemistry 31:11291-6
Browner, M F; Fauman, E B; Fletterick, R J (1992) Tracking conformational states in allosteric transitions of phosphorylase. Biochemistry 31:11297-304
Coats, W S; Browner, M F; Fletterick, R J et al. (1991) An engineered liver glycogen phosphorylase with AMP allosteric activation. J Biol Chem 266:16113-9
Sprang, S R; Withers, S G; Goldsmith, E J et al. (1991) Structural basis for the activation of glycogen phosphorylase b by adenosine monophosphate. Science 254:1367-71
Browner, M F; Rasor, P; Tugendreich, S et al. (1991) Temperature-sensitive production of rabbit muscle glycogen phosphorylase in Escherichia coli. Protein Eng 4:351-7