Abstract

The long term objectives are to understand at the molecular level the recognition of specific sequences of DNA by repressors, and the allosteric modulation of this recognition process by metabolites.
The specific aims are to investigate the thermodynamics and mechanism of the interaction of the trp repressor with its operator DNA and other, non-operator DNA sequences, in the presence and absence of specific modulatory molecules (tryptophan and desaminotryptophan). The repressor protein and the DNA will also be extensively characterized, both structurally and functionally, using advanced high resolution NMR methods, particularly two dimensional techniques and measurements of relaxation times. Once the components have been fully characterized, the changes that occur on forming various complexes will be compared, and detailed information regarding the molecular basis for such recognition will be available. These recognition processes are an integral part of the control of gene expression a topic which lies at the heart of modern molecular biology and relates indirectly to the development of suppression of certain kinds of cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM033385-04
Application #
3283071
Study Section
Biochemistry Study Section (BIO)
Project Start
1985-07-01
Project End
1993-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Finucane, Michael D; Jardetzky, Oleg (2003) Surface plasmon resonance studies of wild-type and AV77 tryptophan repressor resolve ambiguities in super-repressor activity. Protein Sci 12:1613-20
Wang, Yunjun; Jardetzky, Oleg (2002) Probability-based protein secondary structure identification using combined NMR chemical-shift data. Protein Sci 11:852-61
Wang, Yunjun; Jardetzky, Oleg (2002) Investigation of the neighboring residue effects on protein chemical shifts. J Am Chem Soc 124:14075-84
Gryk, M R; Jardetzky, O (1996) AV77 hinge mutation stabilizes the helix-turn-helix domain of trp repressor. J Mol Biol 255:204-14
Gryk, M R; Jardetzky, O; Klig, L S et al. (1996) Flexibility of DNA binding domain of trp repressor required for recognition of different operator sequences. Protein Sci 5:1195-7
Taylor, K L; Strobel, F; Yue, K T et al. (1995) Isolation and identification of a protoheme IX derivative released during autolytic cleavage of human myeloperoxidase. Arch Biochem Biophys 316:635-42
Zheng, Z; Czaplicki, J; Jardetzky, O (1995) Backbone dynamics of trp repressor studied by 15N NMR relaxation. Biochemistry 34:5212-23
Finucane, M D; Jardetzky, O (1995) Mechanism of hydrogen-deuterium exchange in trp repressor studied by 1H-15N NMR. J Mol Biol 253:576-89
Zheng, Z; Gryk, M R; Finucane, M D et al. (1995) Investigation of protein amide-proton exchange by 1H longitudinal spin relaxation. J Magn Reson B 108:220-34
Schmitt, T H; Zheng, Z; Jardetzky, O (1995) Dynamics of tryptophan binding to Escherichia coli Trp repressor wild type and AV77 mutant: an NMR study. Biochemistry 34:13183-9

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